European Association for the Study of Diabetes (EASD) 2016 Annual Meeting

September 12-16, 2016; Munich, Germany; Day #2 Highlights – Draft

Highlights

Guten Tag aus München, where our team has been immersed in Bratwurst, Spätzle, and of course diabetes learning as EASD ramps up into full swing.

See below for our top six highlights from the second day of the 52nd annual EASD meeting, including the conference’s impressive exhibit hall. Be sure to read our preview to learn what’s in store for the remaining three days of the conference, as well as our highlights report from the past two pre-conference days. Also, if you can find spare time in between EASD’s packed schedule of talks, don’t miss our top picks for things to do in historic Munich.

1. A Novo Nordisk poster unveiled the full results of the SUSTAIN 5 trial, which demonstrated superior glycemic control and weight loss for next-generation once-weekly GLP-1 agonist semaglutide versus placebo in patients with type 2 diabetes on basal insulin. The full results shared impressive data on the proportion of semaglutide-treated patients that were able to achieve an A1c target <7%, an A1c target <6.5%, a weight loss of 5% or more, a weight loss of 10% or more, and a composite endpoint of A1c<7% without hypoglycemia or weight gain. We also got a glimpse at semaglutide’s impact on fasting plasma glucose (FPG), mean 7-point self-monitored plasma glucose (SMPG), insulin dose, and blood pressure and saw more granularity on the adverse event data. See our detailed discussion and commentary for a deep dive into these long-awaited positive results. As a preview, 79% (!) of patients on the  1.0 mg semaglutide dose achieved an A1c <7%, compared to 11% with placebo and 61% of subjects achieved an A1c <6.5%, compared to 5% with placebo. Additionally, 66% of subjects on 1.0 mg of semaglutide achieved 5% weight loss, compared to 11% with placebo and 26% of patients taking 1.0 mg dose of semaglutide semaglutide achieved 10% weight loss or greater, compared to 3% with placebo. Wow! 

2. Dr. Bernie Zinman presented long-awaited full results from the ADJUNCT ONE trial of Novo Nordisk’s Victoza (liraglutide) in type 1 diabetes, demonstrating modest reductions in A1c, body weight, and insulin dose and less-welcome increases in adverse events.

3. In a completely packed, at-capacity session, Dr. Stefan Kaspers presented results from two meta-analyses examining the impact of treatment with Lilly/BI’s Jardiance (empagliflozin) on diabetic ketoacidosis (DKA) and bone fracture rates across the body of clinical trial data available. The results were very reassuring overall, demonstrating no clear association between empagliflozin and increased DKA or bone fracture event rates in a clinical trial setting.

4. Dr. Hiddo Heerspink (University Medical Center Groningen, Groningen, the Netherlands) presented a compelling new post-hoc analysis of CANTATA-SU to support a glucose-independent, renal-protective benefit for the SGLT-2 inhibitor canagliflozin (Janssen’s Invokana).

5. Dr. Boris Kovatchev (University of Virginia, Charlottesville, VA) presented a new post-hoc analysis of the phase 3 LixiLan-O trial of Sanofi’s iGlarLixi (insulin glargine/lixisenatide), which found distinct and differential effects of each component agent on fasting and postprandial glucose.

6. Below, we include exhibit hall coverage from 25 companies: 11 diabetes technology booths and 14 diabetes drug booths. Notable booths in tech included Abbott (LibreLink + free sensors), BD (MiniMed Pro set on display), Diasend/Glooko (merged!), Medtronic (Guardian Connect demos), and Roche (Insight CGM on display).

Top Six Highlights

1. A Novo Nordisk poster unveiled the full results of the SUSTAIN 5 trial, which demonstrated superior glycemic control and weight loss for next-generation once-weekly GLP-1 agonist semaglutide versus placebo in patients with type 2 diabetes on basal insulin. As was previously reported in the topline results, adults with type 2 diabetes inadequately managed with basal insulin alone or in combination with metformin (n=397) achieved superior A1c reductions of 1.4% and 1.8% after 30 weeks of add-on treatment with 0.5 mg and 1.0 mg of semaglutide, respectively, compared to a 0.1% reduction with placebo (mean baseline A1c=8.4%, p<0.0001). Semaglutide also demonstrated superior weight loss (3.7 kg-6.4 kg vs. 1.4 kg; baseline = 92 kg), and insulin dose reductions (10%-15% vs. 3%). The full results shared impressive data on the proportion of semaglutide-treated patients that were able to achieve an A1c target <7%, an A1c target <6.5%, a weight loss of 5% or more, a weight loss of 10% or more, and a composite endpoint of A1c<7% without hypoglycemia or weight gain. We also got a glimpse at semaglutide’s impact on fasting plasma glucose (FPG), mean 7-point self-monitored plasma glucose (SMPG), insulin dose, and blood pressure and saw more granularity on the adverse event data. See our detailed discussion and commentary for a deep dive into these long-awaited results.

2. Dr. Bernie Zinman (Mount Sinai Hospital, Toronto, Canada) presented long-awaited full results from the ADJUNCT ONE trial of Novo Nordisk’s Victoza (liraglutide) in type 1 diabetes, demonstrating modest reductions in A1c, body weight, and insulin dose and less-welcome increases in adverse events. The randomized, double-blind, placebo-controlled compared the efficacy and safety of three doses of liraglutide – 0.6 mg, 1.2 mg, and 1.8 mg – to placebo in patients with type 1 diabetes (n=1,398) over 52 weeks of treatment. The trial found a modest, dose-dependent effect for liraglutide on A1c: mean placebo-adjusted reductions were 0.2% with the 1.8 mg dose (baseline A1c=8.14, p<0.05), 0.15% with the 1.2 mg dose (baseline A1c=8.16 mg, p<0.05), and 0.09% with the 0.6 mg dose (baseline A1c 8.16%, non-significant compared to placebo). Dr. Zinman emphasized that the placebo group in the trial also experienced a significant improvement in A1c (of course! It’s a randomized controlled trial!) and the additional liraglutide-associated reductions should be considered in this context. All three doses of liraglutide also produced statistically significant body weight reductions: -4.9 kg (~11 lbs) with the 1.8 mg dose (p<0.05), -3.55 kg (~8 lbs) with the 1.2 mg dose (p<0.05), and -2.19 kg (~5 lbs) with the 0.6 mg dose (p<0.05). Furthermore, treatment with the two higher doses of liraglutide led to modest but statistically significant reductions in insulin dose of about 0.08 units and 0.05 units per unit of insulin compared to the placebo group, respectively (p<0.05 for both). A greater proportion of patients on the two higher doses achieved a composite outcome of an A1c <7% and no severe hypoglycemia compared to placebo as well: 18% of participants were able to achieve this goal in the 1.8 mg dose group (p=0.0024) and 20% of participants were able to in the 1.2 mg dose group (p=0.0003). For comparison, less than 10% of participants in the placebo group were able to achieve this composite goal.

  • The adverse event profile of liraglutide in ADJUNCT ONE raised several potential safety concerns. As expected, nausea was the most common adverse event, the association was dose-dependent, and the nausea rates subsided over time. More worrisome was the 31% increase in symptomatic hypoglycemia in the 1.8 mg group (p=0.0081) and the 27% in the 1.2 mg group (p=0.0219) – symptomatic hypoglycemia was numerically increased in the 0.6 mg group but was not statistically significant. This translated to 16.5 hypoglycemic events per patient year of exposure for the 1.8 mg dose and 16.1 events per patient year of exposure for the 1.2 mg dose. On the other hand, adjudicated confirmed severe hypoglycemia trended lower in the liraglutide-treated groups (hazard ratios of 0.85, 0.61, and 0.64 in the 1.8 mg, 1.2 mg, and 0.6 mg groups, respectively), though the confidence intervals were very wide and none of the differences were statistically significant due to low event rates. Our guess is that the insulin reduction just wasn’t quite enough as the GLP-1 ramped up and we think this could’ve been managed over time. We would’ve been very interested to see the “time in zone” profile had patients worn CGM – we think the trial was done before the best CGM tools were available. Of bigger concern was the more than three-fold, statistically significant increase in hyperglycemia with ketosis with the highest 1.8 mg dose of liraglutide (HR=2.22; 95% CI: 1.13-4.34; p=0.0205). Hyperglycemia with ketosis was also increased in the 1.2 mg and 0.6 mg groups, though the results were not statistically significant. Notably, there were eight episodes of full-blown diabetic ketoacidosis (DKA) in ADJUNCT ONE, all of which occurred in the liraglutide-treated groups (three episodes in the 1.8 mg group, one episode in the 1.2 mg group, and four episodes in the 0.6 mg group). Dr. Zinman noted that all the cases of DKA occurred in patients with no detectable C-peptide levels and suggested in Q&A that liraglutide has differential effects in patients with type 1 diabetes with and without C-peptide, though he acknowledged that the number of patients with C-peptide was too low to conduct a rigorous analysis of this. Overall, however, Dr. Zinman concluded that the safety signals combined with the modest efficacy demonstrated by liraglutide in this trial limits its value and utility in patients with type 1 diabetes – we agree with this although we think the way that outcomes could be done today are different from back then and we do think GLP-1 is still of interest to type 1 patients – but difficult to know how to personalize for which patients and safety issues are definitely greater than we had realized (though some would still want to figure out how to use GLP-1 because the risk/benefit in their view would be worth it). Based on these results, Novo Nordisk announced its decision not to pursue a type 1 diabetes indication for Victoza over a year ago (concurrent with the release of the topline data). At the time, little detail on the adverse event profile was provided. While the increase in hypoglycemia and hyperglycemic ketosis, as well as the decision not to pursue an expanded indication, are very disappointing, we’re intrigued by the possibility of a subset of patients with type 1 diabetes responding better to treatment. We hope that future studies can perhaps dig further into the efficacy and safety of liraglutide among patients with type 1 diabetes and some degree of remaining C-peptide, though we recognize that Novo Nordisk has many other ongoing projects in diabetes on which it is focused.

3. In a completely packed, at-capacity session, Dr. Stefan Kaspers presented results from two meta-analyses examining the impact of treatment with Lilly/BI’s Jardiance (empagliflozin) on diabetic ketoacidosis (DKA) and bone fracture rates across the body of clinical trial data available. The results were very reassuring overall, demonstrating no clear association between empagliflozin and increased DKA or bone fracture event rates in a clinical trial setting. The completely packed, large presentation room and the audience’s rapt attention is a testament to both the interest in the SGLT-2 inhibitor class and the concerns many providers have about the relationship between SGLT-2 inhibitors and these two adverse events. We expect these reassuring results, coupled with the compelling EMPA-REG OUTCOME data demonstrating potential cardioprotective and renal-protective benefits for empagliflozin, might lead to some providers and patients preferring empagliflozin over other SGLT-2 inhibitors in the class (though, of course, many prescribing decisions today are too often dictated by reimbursement and access as well).

  • The DKA meta-analysis found DKA event rates were very low and balanced between empagliflozin-treated and comparator groups, though increased urinary ketones was more common among participants treated with empagliflozin. The analysis was conducted with data from 18 randomized phase 1-3 clinical trials for empagliflozin (including the EMPA-REG OUTCOME cardiovascular outcomes trial) and from six extension studies. The analysis was based on investigator-reported outcomes and included a total of 15,677 patients. In total, the analysis included over 19,000 patient-years of exposure to empagliflozin. The DKA meta-analysis found only 12 cases of DKA in all of the clinical trials combined: 5 events among participants treated with the 10 mg dose of empagliflozin, 2 events among those treated with 25 mg of empagliflozin, and 5 events among those in the comparator groups. The event rate of each of these groups per 100 patient-years was 0.06, 0.02, and 0.05, respectively. 10 of these DKA events were classified as serious, 5 in those treated with 10 mg empagliflozin, 1 in those treated with 25 mg empagliflozin, and 4 in those treated by comparators (events rates were 0.06, 0.01, and 0.04 per 100 patient-years, respectively). Of the seven participants who experienced a DKA event while on empagliflozin, only two discontinued the study drug (none of the five participants who experienced a DKA events on placebo discontinued). The meta-analysis also showed that, based on regular urinary ketone tests from these trials, the vast majority of patients either never experienced a positive ketone test (76% of patients in empagliflozin-treated arms and 82% in comparator arms) or never experienced higher than trace levels of ketones (14%-15% of those in the empaglifozin-treated arms and 14% in the comparator arms. That said, a greater proportion of participants treated with empagliflozin experienced elevated urinary ketones across the studies than those in comparator arms (10% in the empagliflozin-treated arms compared to 4% in the comparator arms).
  • The bone fracture meta-analysis found that the proportion of patients experiencing bone fractures was comparable between empagliflozin-treated groups and comparators overall and in all age, gender, and eGFR subgroups. The bone fracture meta-analysis was conducted with data from 15 placebo-controlled phase 1-3 clinical trials and four extension studies – one trial, the EMPA-REG H2H-SU head-to-head study of empagliflozin vs. sulfonylurea glimepiride, was discussed separately. The main meta-analysis was based on investigator-reported outcomes and included a total of 12,620 patients. The overall bone fracture event rate per 100 patient-years was 1.55, 1.36, and 1.69 with empagliflozin 10 mg, empagliflozin 25 mg, and placebo, respectively (absolute event rates were 2.8%, 2.5%, and 2.9%, respectively). The event rate per 100 patient-years and the absolute rate were similarly comparable across empagliflozin and placebo groups for serious bone fractures (0.38 [0.7%] with empagliflozin 10 mg, 0.47 [0.9%] with empagliflozin 25 mg, and 0.59 [1%] with placebo). For bone fractures leading to discontinuation, the rate per 100 patient-years and absolute rate remained comparable and were even lower across the board (0.08 [0.1%] with empagliflozin 10 mg, 0.10 [0.2%] with empagliflozin 25 mg, and 0.23 [0.4%] with placebo). Bone fractures were similarly comparable regardless of type (upper limb, lower limb, thoracic cage, spinal, skull and facial, pelvic, or other). The subgroup analyses found that bone fractures were more frequent in both empagliflozin and placebo arms among females, increasingly older patients, and those with decreasing renal function. Dr. Kaspers emphasized that within these subgroups of increased risk, bone fracture rates among empagliflozin-treated participants were comparable to rates among the placebo groups. Dr. Kaspers also pointed out that there were no changes in calcium or phosphate levels with empagliflozin or placebo and no notable differences in changes in other bone markers between empagliflozin and placebo groups. Analysis of bone fracture rates in EMPA-REG H2H-SU found similar results regarding the comparability of bone fracture rates between the empagliflozin and glimepiride groups. Furthermore, EMPA-REG H2H-SU included measures of bone mineral density from femoral neck and lumbar spine DXA scans after 52, 104, 156, and 208 weeks of treatment. The results demonstrated that bone mineral density remained stable throughout the four years of empagliflozin treatment and were comparable between those treated with empagliflozin and those treated with glimepiride. We’re certainly glad that the potential relationship between SGLT-2 inhibitors and bone fracture risk does not appear to be a class effect – where it has been seen to date may have been spurious correlation and we look forward to more data all around. As a reminder, the FDA strengthened the label warning on bone fracture risk with J&J’s Invokana (canagliflozin) last year.

4. Dr. Hiddo Heerspink (University Medical Center Groningen, Groningen, the Netherlands) presented a compelling new post-hoc analysis of CANTATA-SU to support a glucose-independent, renal-protective benefit for the SGLT-2 inhibitor canagliflozin (Janssen’s Invokana). The analysis was published recently in the Journal of the American Society of Nephrology. CANTATA-SU was a phase 3, double-blind, head-to-head study of canagliflozin (100 or 300 mg/day) vs. sulfonylurea glimepiride (titrated to 6-8 mg/day) over 24 months in patients with type 2 diabetes (n=1,450) on metformin monotherapy. In the post-hoc analysis, eGFR declines throughout the trial were smaller with both doses of canagliflozin compared to glimepiride (declining 0.5 ml/min in the canagliflozin 100 mg group [p=0.01] and 0.9 ml/min in the canagliflozin 300 mg group [p=0.01], compared to a 3.3 ml/min reduction in the glimepiride group. The results suggest that canagliflozin, compared with glimepiride, slows the progression of renal disease in type 2 diabetes patients over two years. Canagliflozin furthermore produced reductions in urinary albumin:creatine ratio (UACR) compared to glimepiride (5.7% reduction with the 100 mg dose and 11.2% reduction with the 300 mg dose, p=0.01). This was especially pronounced in the subgroup of patients with baseline UACR above 30 mg/g, who experienced a 31.7% (p=0.01) decline in this ratio with canagliflozin 100 mg and a 49.3% (p=0.01) decline in this ratio on the 300 mg canagliflozin dose compared to glimepiride treatment. Further post-hoc analysis revealed that the treatment effect of canagliflozin on albuminuria persisted even after statistically controlling for the differences in A1c reduction, systolic blood pressure, body weight, or the combined changes in all three of these factors between the canagliflozin and glimepiride arms. This suggests that canagliflozin’s effect on albuminuria occurs independently of its glycemic effects – wow! We’re intrigued by the suggestion of renal-protection for canagliflozin demonstrated by these analyses and our curiosity is piqued regarding the mechanism by which SGLT-2 inhibitors achieve this renal-protective effect. Lilly/BI’s SGLT-2 inhibitor Jardiance (empagliflozin) recently demonstrated impressive renal-protective benefits in EMPA-REG OUTCOME and we’re certainly looking forward to more renal outcomes data from other products in the class – as well as for GLP-1 compounds. Diabetic nephropathy is an extremely costly complication of diabetes, both in human and economic terms, and the availability of glucose-lowering drugs with additional renal-protective benefits is a major win for patients. We look forward to hearing more on renal impact of diabetes drugs in the coming days at EASD.

  • An astute comment during the ensuing Q&A session pointed out that this study lacks a sufficient control group. Thus it is impossible to tell whether the renal benefits of canagliflozin over glimiperide are due to canagliflozin being beneficial or glimiperide being harmful. To resolve this issue, we would love to see similarly-designed trials in the future that includes a third, placebo-controlled arm. Also, just in general, we’d love to see SFUs used in more outcomes trials. Though it may make more patients not want to participate in the trials, we think that more data is needed to show the negativity of SFUs – so many patients are forced to be on SFUs still and there is not enough data for patient advocates to try to push back for these patients. For some group of course, lower-dose SFUs may be fine, but we think the combination of weight gain and hypoglycemia and fracture risk and beta cell burnout is quite negative for most.
  • The CREDENCE trial is underway to assess the effects of canagliflozin (100 mg/day) on renal endpoints in patients with diabetic kidney disease. With nearly 4,000 subjects enrolled, Dr. Heerspink explained that the CREDENCE trial will be powered to definitively show whether canagliflozin has renal-protective effects. According to ClinicalTrials.gov, this trial is estimated to complete in January 2020.

5. Dr. Boris Kovatchev (University of Virginia, Charlottesville, VA) presented a new post-hoc analysis of the phase 3 LixiLan-O trial of Sanofi’s iGlarLixi (insulin glargine/lixisenatide), which found distinct and differential effects of each component agent on fasting and postprandial glucose. Initial results from LixiLan-O demonstrated that iGlarLixi treatment produces greater A1c reductions than treatment with insulin glargine (Sanofi’s Lantus) or lixisenatide (Sanofi’s Lyxumia) alone. Dr. Kovatchev positioned this post-hoc as a “deconstruction” of the A1c lowering effect, as the analysis elucidated the specific impact of each drug on fasting and postprandial glucose. Insulin glargine lowered average glucose (mean of seven-point SMBG measures) from 10.2 mmol/l (184 mg/dl) at baseline to 7.7 mmol/l (138 mg/dl) at 30 weeks (a 2.5 mmol/l [45 mg/dl] drop, p<0.0001) and lixisenatide lowered average glucose from 10.4 mmol/l (187 mg/dl) at baseline to 8.5 mmol/l (153 mg/dl) at 30 weeks (a 1.9 mmol/l [34 mg/dl] drop, p<0.0001). When put together as iGlarLixi, the combination lowered average glucose from 10.4 mmol/l (187 mg/dl) to 7.0 mmol/l (126 mg/dl), marking a more substantial 3.4 mmol/l (61 mg/dl, p<0.0001) decline. Dr. Kovatchev noted that this glucose effect is not completely additive, and explained how this indicates some overlap in the type of hyperglycemia (fasting or postprandial) targeted by each component, glargine and lixisenatide. Similarly, the effects of insulin glargine and lixisenatide on glucose variability and glycemic exposure are not completely additive. Patients’ glucose variability, as measured by the High Blood Glucose Index (HBGI), declined by a mean of 6.3 from a baseline of 9.8 if treated with insulin glargine alone, by 5.3 from a baseline of 10.4 if treated with lixisenatide alone, and by 8.3 from a baseline of 10.3 if given iGlarLixi. Glycemic exposure, as measured by area under the curve, fell ~34 mmol-hr/l from a baseline of 144 mmol-hr/l in the glargine group, fell ~27 mmol-hr/l from a baseline of 147 mmol-hr/l in the lixisenatide group, and fell ~48 mmol-hr/l from a baseline of 146 mmol-hr/l in the iGlarLixi group. Using vector analyses of the contributions of insulin glargine and lixisenatide to iGlarLixi’s effect, Dr. Kovatchev suggested that the postprandial effect of lixisenatide might have a greater impact on iGlarLixi’s reduction of glycemic variability than on its reduction of overall plasma glucose. While this information is certainly helpful to theorists and academic researchers, we think “time in zone” data would be more understandable for patients and some HCPs. 

6. Below, we enclose exhibit hall coverage from 25 companies: 11 diabetes technology booths and 14 diabetes drug booths. Notable booths in tech included Abbott (LibreLink + free sensors), BD (MiniMed Pro set on display), Diasend/Glooko (merged!), Medtronic (Guardian Connect demos), and Roche (Insight CGM on display). See the full details below!

Honorable Mention

The diaTribe Foundation's Third Annual Solvable Problems in Diabetes Forum

Tina Vilsbøll, MD (University of Copenhagen, Copenhagen, Denmark) , Lutz Heinemann, MD (Profil Institut, Neuss, Germany), Bernie Zinman, MD (Mount Sinai Hospital, University of Toronto, Ontario, Canada)

Last night, The diaTribe Foundation hosted its third annual "Solvable Problem in Diabetes" forum by welcoming over 150 attendees with drinks, hors d'oeuvres, and great conversation at the historical Isarpost Event Location in downtown Munich. During the panel discussion, we heard so many actionable suggestions on drug therapy and how to amplify the patient voice and visibility of diabetes! We are still compiling our report for those who attended the meeting, but a few of our favorite quotable quotes to tide you over:

  • “Biological pathways are not super highways; the operate like networks. The notion that one drug will be the silver bullet to treat diabetes is unrealistic. Combination therapies will likely be required.” – Dr. Zinman
  • “Libre is a big success story in Germany. Patients loved it even when they had to pay for it themselves, and now insurance companies are starting to cover it. Once the patient voice is involved, things can move forward.” – Dr. Heinemann
  • “Where do things go wrong? We say at a BMI above 30, but maybe we should say things go wrong at BMI >27 and not let diabetes happen. We need to start intervention earlier.” – Dr. Vilsbøll
  • “The government needs to hear a loud voice not from pharma, but from patients with diabetes. Look at what happened with HIV/AIDS – the community knew how to solve that problem by speaking up. The voice of diabetes is not being heard.” – Dr. Zinman

Detailed Discussion and Commentary

Posters

Efficacy and Safety of Semaglutide Once-Weekly vs. Placebo as Add-on to Basal Insulin Alone or in Combination with Metformin in Subjects with Type 2 Diabetes (SUSTAIN 5)

A Novo Nordisk poster unveiled the full results of the SUSTAIN 5 trial, which demonstrated superior glycemic control and weight loss for next-generation once-weekly GLP-1 agonist semaglutide versus placebo in patients with type 2 diabetes on basal insulin. As was previously reported in the topline results, adults with type 2 diabetes inadequately managed with basal insulin alone or in combination with metformin (n=397) achieved superior A1c reductions of 1.4% and 1.8% after 30 weeks of add-on treatment with 0.5 mg and 1.0 mg of semaglutide, respectively, compared to a 0.1% reduction with placebo (mean baseline A1c=8.4%, p<0.0001). Semaglutide also demonstrated superior weight loss (3.7 kg-6.4 kg vs. 1.4 kg; baseline = 92 kg), and insulin dose reductions (10%-15% vs. 3%). The full results shared impressive data on the proportion of semaglutide-treated patients that were able to achieve an A1c target <7%, an A1c target <6.5%, a weight loss of 5% or more, a weight loss of 10% or more, and a composite endpoint of A1c<7% without hypoglycemia or weight gain. We also got a glimpse at semaglutide’s impact on fasting plasma glucose (FPG), mean 7-point self-monitored plasma glucose (SMPG), insulin dose, and blood pressure and saw more granularity on the adverse event data. See below for a deep dive into these long-awaited results.

  • From the full results, we further learned that higher proportions of semaglutide-treated participants achieved their A1c targets and weight loss goals. For participants receiving 0.5 mg and 1.0 mg semaglutide, 61% and 79% achieved an A1c <7%, compared to 11% with placebo (p<0.0001). 41% and 61% of subjects respectively achieved an A1c <6.5%, compared to 5% with placebo (p<0.0001). Additionally, 42% and 66% of subjects given 0.5 mg and 1.0 mg semaglutide achieved 5% weight loss, compared to 11% with placebo (p<0.0001 for both). Furthermore, a higher proportion of participants taking semaglutide achieved 10% weight loss or greater (9% with the 0.5 mg dose [p=0.04] and 26% of patients with the 1.0 mg dose [p<0.0001], compared to 3% with placebo).  Finally, the full results revealed that a significantly higher proportion of subjects achieved the triple goal of A1c <7% without severe or BG-confirmed symptomatic hypoglycemia and without weight gain: 54% and 67% respectively with 0.5 mg and 1.0 mg semaglutide, versus 7% with placebo.
  • New efficacy data also elaborated upon the secondary outcomes of mean fasting plasma glucose (FPG), mean 7-point self-monitored plasma glucose (SMPG), and blood pressure. From a baseline of 8.6 mmol/l (154 mg/dl), mean FPG decreased by 1.6 mmol/l (29 mg/dl) and 2.4 mmol/l (43 mg/dl) in the semaglutide 0.5 mg and 1.0 mg groups, respectively, significant reductions as compared to the 0.5 mmol/l (9 mg/dl) FPG reduction seen in the placebo group (p=0.0002 and p=0.0001, respectively). Furthermore, mean 7-point SMPG decreased by 2.5 mmol/l (45 mg/dl) and 3.0 mmol/l (54 mg/dl) in the semaglutide treatment groups, respectively, significantly more than the 0.8 mmol/l (14 mg/dl) reduction observed in the placebo group (p=0.0001 for both). Postprandial increments for mean 7-point SMPG also decreased significantly more in the 0.5 mg and 1.0 mg semaglutide groups (-0.8 mmol/l [14 mg/dl] and -1.2 mmol/l [22 mg/dl], respectively), versus a 0.2 mmol/l [4 mg/dl] reduction in the placebo group (p=0.003 and p<0.0001, respectively). The larger 1.0 mg semaglutide dose was significantly more effective at reducing systolic blood pressure than placebo (-6.29 mmHg; p=0.0007). The 0.5 mg semaglutide dose also reduced systolic blood pressure, but the reduction was not significantly different from that seen with placebo.
  • Over the 30-week trial, insulin dose decreased in all treatment doses. Overall, subjects on semaglutide 0.5 mg and 1.0 mg decreased their insulin dose by 10% and 15%, versus 4% in the placebo group (p=0.0046 and p<0.0001, respectively, compared with placebo). Among patients with A1c >8.0% at screening, the semaglutide 0.5 mg and 1.0 mg groups reduced their insulin dose by 6% and 10%, versus 2% with placebo. Patients with A1c <8.0% at screening mandatorily reduced their insulin dose by 20% at the beginning of the trial to minimize hypoglycemia risk. By the end of the trial they had reduced their insulin dose from baseline by 18% and 24% with semaglutide 0.5 mg and 1.0 mg, versus 7% with placebo.
  • New safety data revealed that subjects given semaglutide 0.5 mg, 1.0 mg, and placebo experienced adverse events (AEs) in the proportions of 69%, 64%, and 58%, respectively. 6.1%, 9.2%, and 6.8% of subjects respectively reported serious AEs across multiple organ classes, and 4.5%, 6.1%, and 0.8% permanently discontinued treatment due to AEs. Treatment with 0.5 mg and 1.0 mg semaglutide increased pulse rate by 1 and 4 beats per minute, respectively; by contrast, placebo decreased pulse rate by 1 beat per minute. No event adjudication committee (EAC)-confirmed pancreatitis events or fatal events were reported, but there were four instances of gallbladder disease and one instance of EAC-confirmed malignant neoplasm among the semaglutide-treated groups.
    • As expected, the most frequent AEs in semaglutide-treated subjects were gastrointestinal, and mild to moderate in nature. 11.4% and 16.8% of subjects treated with 0.5 mg and 1.0 mg semaglutide reported nausea, as compared to 4.5% of subjects on placebo.
    • Severe or BG-confirmed symptomatic hypoglycemia occurred in 8.3%, 10.7%, and 5.3% of subjects treated with semaglutide 0.5, 1.0 mg and placebo. The proportions of subjects experiencing hypoglycemia were comparable between the semaglutide and placebo groups among patients with A1c >8.0% at screening, but among patients with A1c <8.0%, hypoglycemia occurred in a higher proportion of the semaglutide-treated groups. We think that is manageable – this is expected given people had to reduce insulin and that’s always a bit tricky (in the “real world” of course more people would go on this drug before going on to insulin).
  • Semaglutide is poised to become Novo Nordisk’s star GLP-1 agonist once the patent for the hugely-successful Victoza (liraglutide) expires. This new evidence demonstrating the safety and efficacy of semaglutide in combination with basal insulin therapy indicates that the drug has a promising future in store, and enhances our anticipation for Friday’s announcement of the SUSTAIN 6 trial results, assessing cardiovascular outcomes for semaglutide. 

Exhibit Hall – Diabetes Technology

Abbott

Upon entering the exhibit hall, Abbott’s setup immediately caught our eye with shiny yellow branding and a lengthy queue of people waiting to take home their very own (free) FreeStyle Libre sensors. The company also focused heavily on the LibreLink Android app (currently available in Sweden, the Netherlands, Germany, Italy, and the UK) – as we arrived, a packed lecture about the app was just wrapping up in the middle of the exhibit, and the buzz was extremely positive as attendees filed out. The clever “You Can Do It” marketing campaign was extended to LibreLink: “Patients can do it with their phone,” featuring a cyclist happily swiping the Libre sensor. This is a very appealing campaign. As expected, Abbott reps did not have any updates for us on the FDA status of either the Libre Pro (approval expected imminently per the 2Q16 financial update) or the consumer version (yet to be submitted to the FDA, to our knowledge), but were very enthusiastic about yesterday’s Lancet publication of data from the IMPACT trial and partnerships with mySugr and Social Diabetes (see our Day #1 report). In terms of presentation, one corner of the booth featured a touchscreen with rotating pictures of people and their accompanying testimonials about the Libre. Our personal favorite? “Just keep calm, flash and carry on!!”

Ascensia

Ascensia’s futuristic, white booth mainly focused on the Contour Next One Bluetooth-enabled BGM – currently available in Switzerland and Poland, with more EU launches planned for later this year (it was cleared in May). We got to demo one of the meters ourselves (using sugary food coloring), and then explore the Contour app both in real life and in virtual reality. For the latter, a rep situated us in a sound-dampening egg-shaped chair and fitted us with VR glasses, and we were transported to what looked like a typical den, only with a giant floating app interface before us. We were led through the process of testing our blood glucose, logging a picture of the sushi that we had just “eaten,” and examining a trend graph. Cool! Even though the app hasn’t reached holographic status just yet in the real world, we still commend Ascensia for it’s easy-to-use interface.

BD

BD’s showed off its most highly anticipated pipeline product (with partner Medtronic), the MiniMed Pro-set with BD FlowSmart technology – this was the first time we’ve seen it on European soil, and only the second time in an exhibit hall (following AADE last month). Reps maintained that the set is slated for a limited (at least 1,000 patients) launch in the US and France to collect user feedback in the next month or so, followed by a full-scale, global launch around December. New to us was the soon-to-be launched patient education website “BD and Me.” The site intends to “bring diabetes education to life” by offering eight online video courses on the newly released FITTER-based injection recommendations. This is excellent to see, as one of the main comments on the recent FITTER publications (Mayo Clinic Proceedings) noted the challenge of wide dissemination – we’re going to be so happy to write about this on our patient website diaTribe.org! There are so many learnings from FITTER that we think so many patients don’t know (as well as HCPs) so this should be very positive. Starting this December in the UK, and soon thereafter in other countries (eventually it will be global), providers will be able to refer patients to these video lessons for quick and easy instruction and refreshers – nice! In light of FITTER’s commentary on needle length and sharps disposal, the booth also had a demo table with the compelling AutoShield safety 4-mm pen needles – we continue to see this as an example of very meaningful “low tech” innovation that still makes a huge difference for patients.

Dexcom

Dexcom’s sported a small but busy booth with a lineup of iPhones displaying the G5 app. Handouts highlighted the positive CGM reimbursement decision in Germany (see our June coverage), though despite Dexcom’s press release last week (that was a bit confusing to us), we confirmed that the company still has to negotiate pricing and contract with payers – but hearing that it will be reimbursed in Germany was a massive win! Dexcom’s 2Q16 call noted that a revenue impact from German reimbursement won’t come until 2017, and we assume that is still the case. Nevertheless, this news has been referenced in many sessions at EASD and is a tremendous victory for the field in one of the world’s most challenging reimbursement environments. In short, it is a statement that says CGM is cost-effective, and hopefully a sign of more positive things to come in other markets. Abbott’s cash-pay FreeStyle Libre has done very well in Germany, an indication that demand is high for easy and convenient and discreet glucose sensing and eliminating fingersticks. This positive decision for CGM will clearly expand the German market, and we look forward to seeing the size of its impact on Dexcom’s still fairly small international sales base (~13% of sales in 2Q16 – so much room for upside!).

Diasend/Glooko

The modestly sized booth boasted the major tech news of the day: Diasend has merged with Glooko to form a unified company under the Glooko name and headed by Glooko CEO Rick Altinger. The two Diasend reps and one Glooko rep at the booth were up for discussing the merger, which was great – it is aimed at building the “World’s Premier Diabetes Management Platform.” The merger is incredibly symbiotic in nature in our view – Diasend brings existing integration with 140+ devices, a sizable global footprint (23 countries), and reimbursement expertise in a wide variety of markets, while Glooko brings strong user interface, great data analytics and reporting, and population tracking. See our detailed thoughts on the merger and an interview with the Glooko and Diasend teams.

Emperra

The tiny booth sported the recently launched Bluetooth-enabled, reusable Esysta connected pen. According to the rep, the pen is reimbursed by insurance in Germany, though the cash pay price is very expensive: 192 euros for a single pen and 616 euros (!) for a pen and meter. The company says it works with any insulin, as plastic adaptors convert any insulin cartridge to fit in the pen. We thought these were clunky and did not find them confidence inspiring (picture below). The button on the pen was more difficult to press down than manual pens, though we liked that the dose calculator gave a countdown timer on screen. We are elated to see more interest in Bluetooth-enabled pens, though are not confident that Emperra is the real deal at this stage. See our August coverage of Companion Medical’s FDA clearance for a smart pen/cap landscape review.

 

EOFlow

New to us, Korea-based EOFlow showed off a disposable patch pump, EOPatch. It looks similar in size to the original OmniPod and communicates with a snappier looking handheld touchscreen controller. According to the company’s two-line press release last week, the pump has been submitted for verification and validation and will be available “in the global market in 2017.” The on-body patch and handheld do have Bluetooth and can communicate with CGM. According to the EOFlow’s website, the company started at a university incubation center in Seoul, Korea in 2011. The booth and website are not confidence inspiring, though we’ll be interested to see if the product is indeed commercialized. The pump market is very competitive and not for the faint of heart …

Inside Biometrics

We stopped by the Inside Biometrics booth to have a first look at the Bluetooth-enabled Keya Smart System, a meter that measures both blood glucose and ketone levels using the same strip. The device is about the size of a pack of cards (see picture below), has a very easy-to-use interface, and functions like a normal BGM, but alerts operators when their ketones are high. It received a CE mark back in May, and a UK launch is expected by the end of the year, with Germany to follow soon thereafter. FDA clearance is expected next year, though it has not yet been filed. Reps told us that the company has an existing integration agreement with Diasend (now merged with Glooko), and is working on an app that would offer actionable analytics – they seemed particularly excited about this because so little is known about the interactions between glucose and ketone levels. When asked about the possibility of a flash or continuous monitoring system, reps told us to keep an eye out for gen 2. Inside Biometrics will soon be ramping up, growing their team from ~45 to ~60 people, outsourcing manufacturing of the meter (but not the strips), and establishing a branch in California. BGM is a very tough market for startups, but we are happy to see some novel innovation and a product that could conveniently address DKA – most patients don’t even know what their ketone levels should be, let alone have the supplies to measure them – and the issue is important as SGLT-2s are used in type 1. We like the convenience of a normal meter that can measure ketones in the background, reducing the hassle of Abbott’s Precision Xtra meter that requires separate strips.

  • Reps were thrilled with the reception from the EASD crowd. The small booth was frequently busy, Dr. Lutz Heinemann gave the meter a shoutout during an oral session, and the reps related that some unspecified pharma companies had asked them if they could perform a trial with the meter, while other companies approached them with hopes of assisting in the development of the app. 

Kaleido

We first saw Kaleido at last year’s EASD, and the company received a CE Mark earlier this year. The very colorful patch pump is expected to launch in the Netherlands and UK by the end of this year. The approach resembles Cellnovo, giving patients two reusable pump units, a wireless controller handheld, and an insulin cartridge that connects to a short on-body infusion set (5 cm or 30 cm). Unlike Cellnovo or the OmniPod, the handheld doesn’t have a built-in blood glucose meter, though the company recently added a bolus calculator. The body-worn pump and iPod-like handheld are both quite slim (measurements here), and the company has put a major emphasis on customizable color offerings. This is direct competition for Cellnovo, who has had a fairly slowly launch ramp in Europe.  

Medtronic

Medtronic’s booth focused overwhelmingly on demoing Guardian Connect, it’s CE Marked Bluetooth-enabled, standalone CGM. Reps said the product will launch in Europe in mid-November, on the very early side of the updated timing shared in the 2Q16 call (~Nov 2016-Jan 2017). The booth had scores of Apple devices running the Guardian Connect iOS app, which has a very clean interface and design that will give Dexcom’s G5 a competitive run for its money. We learned that the Bluetooth-enabled transmitter will backfill up to eight hours of data if the phone is out of range, on par with FreeStyle Libre. The Guardian Connect app will launch initially on iOS in Europe with a “Today” widget (swipe down from the home screen to view data – essential for patient convenience in our view), though it will not initially post to HealthKit or have a Watch app. “Care Partners” will be able to get customizable text message notifications for out-of-range values, including predicted lows and highs. As a reminder, this will launch with Enlite 2 (Enlite Enhanced) outside the US; the US version of Guardian Connect with Enlite 3 is currently under FDA review, with launch expected by April 2017. The MiniMed 640G – now available for more than a year outside the US – was a minor part of the booth, but still drew some interest from curious attendees. Patients on the 640G we’ve run into here absolutely love it, and it has certainly shown in Medtronic’s recent international revenue performance. 

POCTech

China-based POCTech was back again at this EASD, advertising a seven-day, Bluetooth-enabled CGM requiring just one calibration per day. A handout boasted a 9.6% MARD vs. fingersticks in a 73-patient study in two medical centers – there were not enough study details listed to know if the trial was robust, though we assume it was not based on the sparse information and amateur handout. The product actually has a CE Mark in Europe, though the company has resubmitted to update the transmitter to add Bluetooth (approval expected by end of year). The company is seeking a European partner to go to market following approval. The CGM is under review in China for use in the hospital, though the rep said it is 6+ months away from approval (behind the EASD 2015 expectation for Chinese approval by the end of 2016).

Roche

We were delighted to see Roche demoing its soon-to-launch Accu-Chek Insight CGM, branded as “the 7th sense that helps your patients get it right.” Insight is currently in CE Mark approval trials and on track to launch in Denmark, Sweden, the Netherlands, and Norway by the end of the year (see our Day #1 coverage). This initial limited launch (at specialized diabetes centers) will last 6-9 months so that Roche can gather feedback before fully rolling it out in more countries in 2017. In person, the on-body transmitter appeared bulky to us (roughly ~2x the size of Dexcom’s G5), and the single-use inserter was a little intimidating (though reps cited data suggesting otherwise). The preliminary accuracy data presented yesterday, however, was encouraging (MARD: 10.5%), and it will be interesting to see how uptake goes in the increasingly competitive EU market (Abbott FreeStyle Libre, Dexcom G5, Medtronic Guardian Connect, Senseonics Eversense). The Bluetooth-paired app is, at the moment, limited to a dedicated Android phone solely used for the Insight CGM, which is obviously a complete hassle – reps noted that this is only temporary, and iOS and Android apps should be available by the end of the year. The CGM data will not sync with mySugr at launch, but it will eventually if all goes as planned.

  • Roche also showed off the Smart Pix software, a platform to visualize and analyze Insight CGM data. The display contains an AGP-like trace, and a CGM traffic light system that indicates degree of success in a number of categories pertinent to glycemic control over a two-week period. Smart Pix also has what looked like a standard high/low pattern-recognition feature. A rep commented that pilot users’ only complaint was that other meters won’t integrate with it.

Ypsomed

Ypsomed’s expansive green booth deftly balanced demos of the tubeless mylife OmniPod and its own touchscreen durable YpsoPump. According to the rep, the YpsoPump is currently launching in the Netherlands and UK, with Germany expected later this year – this is right on with the timing shared in June when the pump received EMA approval for use with Novo Nordisk’s NovoRapid prefilled insulin cartridges. We had a chance to demo the pump and speak with a patient using it, and both experiences left us positive on the key features: (i) prefilled NovoRapid insulin cartridges for faster set changes (about 15 seconds to load and prime); (ii) touchscreen (capacitive) with an OLED display that is easy to see in the dark; (iii) a fully icon-driven display that has no words (language neutral for Europe); (iv) very light weight (83 g) and small size in the hand; and (v) built-in Bluetooth. Read our full list here of the pump’s strengths, weaknesses, opportunities, and threats.

Exhibit Hall – Drugs

AstraZeneca

AstraZeneca’s sizeable maroon and gold booth was certainly one of the exhibit hall’s most interactive displays. At one corner, an artist stood before a crowd of people, sprinkling white sugar over a glass panel and, in a clever play on the pharmacological idea of glucose removal, effortlessly whisked the sugar away to create elaborate designs. Adjacent to this was a popular game involving detailed figurines of patients that visitors could place on a high-tech glass table, which would light up to reveal that individual’s unique diabetes profile, as well as how they could benefit from AZ’s selection of diabetes drugs. Approximately equal square footage was dedicated to the SGLT-2 inhibitor Forxiga (dapagliflozin), the DPP-4 inhibitor Onglyza (saxagliptin), and the GLP-1 agonist Bydureon (exenatide once weekly), with some mention of Xigduo (dapagliflozin/metformin) and the anti-platelet drug Brilique (ticagrelor) as well. Across the booth, beneath a commanding archway entirely composed of flatscreens panning through the logos of AZ’s impressive lineup of diabetes and cardiovascular therapies, was a bustling coffee bar and lounge area. Signage declared AZ’s excitement about its “next wave of scientific innovation” – a nod to the company’s impressive lineup of emerging diabetes therapies, including the antiplatelet agent Brilinta (ticagrelor), the phase 1/2 PCSK9 inhibitor/GLP-1 agonist combination MEDI4166, and a saxagliptin/dapagliflozin fixed-dose combination (just approved in Europe under the trade name Qtern). Furthermore, colorful dangling panels declared AZ’s commitment to “understanding the cardiovascular and renal profile” of diabetes specifically. This is certainly a timely message at what promises to be a CVOT and renal outcomes-heavy EASD, and in an era when diabetes drugs must offer benefits beyond glycemic reductions in order to set themselves apart.

GI Dynamics

GI Dynamics occupied a small booth near one edge of the exhibit hall. A large painting as well as two 3D models displayed how the EndoBarrier therapy for obesity acts on the stomach. Three clinical effects of EndoBarrier relevant to the treatment of both diabetes and obesity were listed on the wall: (i) restores healthy glycemic levels; (ii) produces significant weight loss; (iii) lessens cardiovascular risk. Many different informational handouts were also available, including one that described EndoBarrier as the first endoscopically-delivered treatment for patients with type 2 diabetes and obesity. The obesity market is challenging and we wish it were easier for companies doing the very hard work to try to help patients on this front.

GSK

GSK’s booth was small and off to a side wall of the exhibit hall. The entire booth was essentially a medical affairs stand with no outright promotion of the company’s one diabetes product, GLP-1 agonist Tanzeum (albiglutide).

Intarcia

Intarcia’s well-sized booth featured two stations demonstrating implantation of the company’s Medici subcutaneous osmotic mini-pump drug delivery system (the device used to deliver a continuous stream of GLP-1 agonist exenatide in the company’s phase 3 ITCA 650). In between these two stations, a spinning, lighted glass case showcased the matchstick-sized mini-pump. The booth with its intriguing demonstration and bold, colorful graphic designs drew a steady stream of curious attendees. It’s clear that Intarcia’s booth is very much focused on attracting potential partners for future applications of the Medici system: the back wall of the booth stated that the company is looking to identify proteins, peptides, antibody fragments, and “other high potency small molecules” suitable for delivery via the system – this is very exciting from our view. Interestingly, the materials also emphasized that the company is particularly interested in oncology, inflammatory diseases, and metabolic disorders (in that order) – we’re a little surprised that oncology would come first in promotional materials at a diabetes conference, though perhaps it is not too surprising that the company is looking to diversify beyond diabetes given the current challenging payer environment and high bar for new diabetes drugs – this is all speculative at this point. There has never been higher interest in increasing adherence and all eyes are on Intarcia as it moves toward regulatory approval.

J&J/Janssen

Like last year, Janssen’s tile-floored exhibit emphasized clinical data showing SGLT-2 inhibitor Invokana’s (canagliflozin) superiority over DPP-4 inhibitor Januvia (sitagliptin). These results and claims were displayed prominently – superior A1c reductions vs. sitagliptin, greater improvements in blood pressure and weight loss vs. sitagliptin, well-tolerated with low frequency of hypoglycemia (~4% of patients treated with Invokana as monotherapy or with Invokana added on to metformin as dual therapy). The exhibit also featured interactive iPads and bright monitors with patient stories on both Invokana and Invokamet (canagliflozin/metformin), calling on people to “change the conversation” surrounding diabetes. Overall, Janssen didn’t seem to deviate very much from what we’ve seen of the company’s exhibit hall presence at other recent conferences, whether US-based or international, although there was less overt promotion of the Check Your Numbers Tracker App compared to ADA 2016 and AADE 2016.

Lilly

Lilly’s large booth was summed up by the large projection of the tagline “A wide range of therapies” projected on the back wall of the booth, just behind the popular espresso bar – indeed, they have the broadest portfolio around! Approaching the booth, the space was flanked with sections devoted to its GLP-1 agonist once weekly Trulicity (dulaglutide) and its BI-partnered SGLT-2 inhibitor Jardiance (empagliflozin), followed by sections devoted to BI-partnered basal insulin Abasaglar (biosimilar insulin glargine), BI-partnered DPP-4 inhibitor Trajenta (linagliptin), and mealtime insulin Humalog, finally culminating in sections devoted to support programs for type 1 diabetes and observational studies. The Jardiance, Trajenta, and Abasaglar sections were essentially miniaturized versions of their space in the Lilly/BI joint booth next door (see below). The purple-and-green Trulicity section evoked the colors of the products extremely patient-friendly IDEO-designed pen while the Humalog section emphasized the product’s 20 years (!) on the market. We were particularly impressed by the “Streetwise” educational materials within the “Support for Type 1 Diabetes” section aimed at young adults living with diabetes – the pamphlets touched on a wide range of topics from exercise and traveling with diabetes to body piercings/tattoos, drinking, and emotional well-being with diabetes. We think the Trulicity app is really something and expect to see it highlighted more in the future.

Lilly/BI

Lilly/BI’s joint booth featured its signature wood-paneled rustic-chic aesthetic in full force – complete with long communal wood picnic tables in which participants could rest on their “hike” through the partnership’s diabetes products. The booth was anchored on one side by biosimilar insulin glargine Abasaglar and on the other by the Jardiance (empagliflozin) SGLT-2 inhibitor and the Trajenta (linagliptin) DPP-4 inhibitor franchises. On the Abasaglar side, Lilly/BI likened insulin initiation to an airplane flight, extolling the virtues of an Abasaglar patient support kit – with injection guides and other educational materials – to ease the “turbulence” of insulin initiation. Further playing on this theme, the area featured several colorful suitcases with stuffed baby animals (the area also featured large pictures of baby animals and the inviting opener “Now that we’ve got your attention…”) and with clinical trial findings on how to ease the anxieties surrounding insulin initiation that many patients face. On the other side, the section devoted to Jardiance and combination Synjardy (empagliflozin/metformin) featured a beanbag toss game highlighting the connection between diabetes and cardiovascular events. The Trajenta and Jentadueto (linagliptin/metformin) section featured futuristic virtual reality headsets (these seem to be popping up everywhere in exhibit halls!) with which participants “walked” through a landscape with pop-up text emphasizing the products’ administration simplicity and its effectiveness at different stages of renal function.

MSD

MSD’s exhibit very much celebrated the 10th anniversary of DPP-4 inhibitor Januvia (sitagliptin), first introduced in 2006. One large wall proudly announced this 10th anniversary and in bold, eye-catching text, emphasized our extensive experience with Januvia as well as the product’s reliable safety profile. Curving teal carpets surrounded a round hardwood floor at the center of the company’s large, open space. The exhibit featured informational handouts on what it means to be an incretin-enhancer, among other topics, and the slogan “Support your patient with confidence. Choose Januvia first as a partner to metformin.” The highlight of MSD’s booth was a high-tech, hologram-like display in one corner explaining how incretins relate to the pathophysiology of type 2 diabetes. We weren’t surprised that the company (Merck’s international equivalent) chose to underscore familiarity and safety as advantages to Januvia, especially with many other exhibits comparing products from newer drug classes to sitagliptin. We were interested by the offering of more general, scientific background on incretin-based drugs (which includes both DPP-4 inhibitors and GLP-1 agonists). There is great interest in Merck’s work ahead with Pfizer on the SGLT-2 and DPP-4/SGLT-2 combination fronts.

Mylan

Mylan boasted a decently-sized booth, swathed in the company’s typical light blue and white color scheme. As a nod to EASD’s thematic emphasis on the cardiovascular complications of diabetes, the booth’s signage was mostly dedicated to Mylan’s cardiovascular drugs, including Lipanthyl (fenofibrate) and Cholib (fenofibrate/simvastatin) for cholesterol and Verapamil (isoptin) for hypertension. To signify the company’s impending entrance into the diabetes arena, touchscreen displays featured descriptions of the  INSTRIDE 1 and INSTRIDE 2 trials of Biocon-partnered biosimilar insulin glargine in type 1 and 2 diabetes showing that the trial met its primary and secondary endpoints. If approved, this biosimilar insulin glargine will be the third-to-market biosimilar insulin glargine in the US. We were disappointed to see no trace of Mylan’s Biocon-partnered development programs for oral Insulin Tregopil, biosimilar insulin aspart (Novo Nordisk’s NovoLog), or biosimilar insulin lispro (Lilly’s Humalog). The periphery of the booth was occupied by towering signs showing images of the diverse range of patients taking Mylan’s drugs. “How do we care for 7 billion people? One person at a time,” the panels read. While some Americans speculated that this strong, patient-centric messaging may be a strategy to rebuild the company’s reputation in the aftermath of the recent outrage over the pricing of Mylan’s EpiPen, we doubt this given the timing needed to create this material – on the other hand, they certainly need something to help. We think patient outrage over pricing generally speaking is only going to become further intensified.    

Novartis

Novartis divided its expansive exhibit into one half dedicated to DPP-4 inhibitor Galvus (vildagliptin) and the other focused on Lucentis (intravitreal ranibizumab) – though the latter was far flashier. The company promoted its diabetic macular edema drug alongside ViaOpta DETECT, a platform to enable early identification of eye complications and referral of patients for timely intervention. A slogan for the platform was featured prominently: collaborate, educate, screen, refer. Notably, by putting on black goggles, you could partake in a virtual reality experience, seeing the world as someone with diabetic retinopathy would. Meanwhile, a large monitor showed what the person in virtual reality was seeing. This attraction drew much attention from conference attendees walking through the exhibit hall, who then stayed to learn more about the fight to preserve vision through interactive monitors and colorful displays. In fact, the crowd at Novartis’ exhibit rivaled that of Novo Nordisk directly adjacent. While more understated, the side of the booth dedicated to DPP-4 inhibitor Galvus was also highly interactive. Patient case stories emphasized the message that when time is running out, patients with diabetes should turn to Galvus. The dominant image of an hourglass on the wall was a powerful, memorable reminder of the time theme.

Novo Nordisk

Novo Nordisk’s commanding booth dominated the exhibit hall, in terms of both attendance and square footage. Approximately equal space was dedicated to Tresiba (basal insulin degludec), Xultophy (insulin degludec/liraglutide), and Victoza (liraglutide), each of which boasted a semi-circular theater area with low slung white benches, a large touchscreen display, and a color-coordinated team of Novo Nordisk representatives giving an interactive presentation on each drug’s efficacy, action profile, and dosing information (all three had a line of physicians waiting to be seated!). The green Tresiba displays advertised the drug’s ability to “get A1c down with control,” a notion that was echoed in the imagery of parachutes “falling” along with A1c. The bright pink Xultophy displays framed the drug as “a step further with one injection per day,” itemizing three of the new drug’s most important benefits: (i) easy; (ii) confident drug delivery ratios; and (iii) preferred by patients.” It’s smart in our view to emphasize composite benefits – that worked very well for liraglutide when building the GLP-1 market (Victoza is now Novo Nordisk’s biggest product!)  The emphasis on Tresiba and Xultophy reflects Novo Nordisk’s clear enthusiasm for its new arrivals, but Victoza received a great deal of attention as well. Sleek maroon signage emphasized Victoza’s status as the “most prescribed GLP-1 agonist” and, perhaps as a nod to the increasing competition in the GLP-1 space, highlighted its “seven years of experience” on the market.

Sanofi

Sanofi’s sleek, white and green booth was one of the exhibit hall’s largest and most well-attended. As was true at recent conferences and last year’s EASD, Toujeo (insulin glargine U300) was the clear focal point, dominating 90% of the booth’s square footage. Signage reminded the booth’s visitors that Toujeo has a “more stable and prolonged action profile than Lantus,” subtly encouraging physicians to switch their patients from the dominant (and off-patent) Lantus to a regimen involving the similar but more advanced Toujeo. We certainly continue to hear great enthusiasm for both Toujeo as well as Novo Nordisk’s next-gen basal insulins. Sanofi’s booth functioned as a thriving social space, with modern white workstations bustling with physicians and a packed movie theater area showing a short film titled “The Challenge,” depicting a group of people with diabetes on a rugged, five-day mountain climbing expedition. Wow! The story was intended to parallel the challenge of combatting diabetes stigma – a message that certainly resonated with us! Two small podiums at the very edge of the booth highlighted Lantus (insulin glargine) and Lyxumia (lixisenatide), but these drugs are clearly not the emphasis of Sanofi’s EASD advertising campaign, presumably due to Lantus’ patent expiry and the fact that Lyxumia is not available in Germany.

Sanofi/Regeneron

Regeneron displayed a decently-sized booth near the entrance to the exhibit hall, dedicated entirely to its PCSK9 inhibitor Praluent (alirocumab). A small crowd was clustered in the booth’s intimate seating area, surrounded by towering, six foot tall statues of blue and green arrows, pointed down toward the ground to parallel Praluent’s LDL cholesterol-lowering action. Signage surrounding the booth’s perimeter emphasized Praluent’s efficacy and ease of use, posting large statistics boasting the drug’s “more than 60% LDL reduction” and the fact that “up to 80% of patients achieved their goal” when taking Praluent. With an eye toward personalization, Regeneron’s advertisements also emphasized the fact that Praluent comes in two different pens, a 75 mg/dl dose and a 150 mg/dl dose for “more power if you need it.”

Takeda

Takeda’s booth stood out at this year’s exhibit hall, with its playful puzzle theme and emphasis on the patient’s point of view. Colorful puzzle pieces – red, purple, neon green – were suspended from the ceiling. Conference attendees were invited to align their feet with footprints on the carpet to symbolize adopting a patient’s perspective, and from that angle exactly, you could see that four hanging puzzle pieces together made-up a photograph of a patient’s smiling face. The company seemed to be highlighting its investment in fulfilling the most pressing patient needs with DPP-4 inhibitor Vipidia (alogliptin, Nesina in the US), Vipdomet (alogliptin/metformin, Kazano in the US), and Incresync (alogliptin/pioglitazone, Oseni in the US). On-theme, even the coffee break tables within the exhibit were shaped like puzzle pieces, and a catchy slogan for Vipidia read “Every piece counts.”

-- by Adam Brown, Abigail Dove, Helen Gao, Brian Levine, Payal Marathe, and Kelly Close