Memorandum

Outcome Trial Competitive Landscape – December 29, 2021

The tables below contain the status, key baseline characteristics, and most notable endpoint results of major diabetes and obesity CVOTs, organized by therapy class. These tables contain both reported and ongoing trials and will be updated as data become available. For more information, trial names link to Close Concerns’ reports on each readout, and we have also included the primary outcomes papers when available. If you’d like additional detail on any of these studies, just ask! We have tried to be as thorough as possible, but if you see anything inaccurate below, please let us know that as well.

  • Latest updates as of December 29, 2021: The expansive growth in outcomes trials in recent years has moved the field (and our landscape!) well beyond the cardiovascular realm. It is always fascinating to recall that these CVOTs began to ensure that glycemic lowering agents were causing no harm, and in doing so, revealed the massive benefits that these therapies could have on other outcomes. We’ve since expanded our competitive landscape to include kidney, heart failure, and obesity outcomes trials. Obesity is, perhaps, one of the areas that we’re most excited about, and we’ve updated the landscape to include the results from the most recent STEP trials (5 and 8) that show the 104-week data of semaglutide 2.4 mg and its efficacy compared to liraglutide, respectively. We also want to draw your attention to the newly announced SURMOUNT-MMO trial, which will assess the effect of tirzepatide on morbidity and mortality in patients with obesity and remind you of the forthcoming OASIS trial (high dose semaglutide) that is expected to complete in 2023 and the SURMOUNT-1 trial (tirzepatide), for which we could see preliminary data later in 2022.

Major Cardiovascular Outcomes Trials

SGLT-2 Inhibitors

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

EMPA-REG OUTCOME for empagliflozin (Lilly/BI’s Jardiance) (outcomes paper)

Completed – reported EASD 2015

7,020

>99%

Age: 63

BMI: 31

A1C: 8.1%

Diabetes Duration: >8 years (57% >10 years, 25% 5-10 years, 18% <5 years)

3.1 years

No other SGLT-2 inhibitors

14% RRR

(HR=0.86, 95% CI: 0.74-0.99, p=0.038 for superiority, p<0.001 for non-inferiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: 38% RRR

(HR=0.62, 95% CI: 0.49-0.77)

All-Cause: 32% RRR

(HR=0.68, 95% CI: 0.57-0.82)

Indication for reducing CV death approved by FDA December 2016

Heart Failure: 35% RRR

(HR=0.65, 95% CI: 0.50-0.85)

CANVAS for canagliflozin (J&J’s Invokana) (outcomes paper)

Completed – reported ADA 2017

10,142

66%

Age: 63

BMI: 32

A1c: 8.2%

Diabetes Duration: 14 years

2.4 years

(5.7 years in CANVAS vs. 2.1 in CANVAS-R)

No other SGLT-2 inhibitors

14% RRR

(HR=0.86, 95% CI: 0.75-0.97, p=0.0158 for superiority, p<0.0001 for non-inferiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

 

CV: NS

(HR=0.87, 95% CI: 0.72-1.06)

All-Cause: NS

(HR=0.87, 95% CI: 0.74-1.01)

~doubled risk for lower-limb amputations with canagliflozin (HR=1.97, 95% CI: 1.41-2.75, p<0.001); CV indication requested October 2017

 

Heart Failure: 33% RRR

(HR=0.67, 95% CI: 0.52-0.87)

 

DECLARE for dapagliflizon (AZ’s Farxiga)

Completed – reported AHA 2018

17,276

41%

Age: 64

BMI: 32

A1c: 8.3%

Diabetes Duration: 12 years

4.2 years

No other SGLT-2 inhibitors, pioglitazone, or rosiglitazone

17% RRR

(HR=0.83, 95% CI: 0.73-0.95, p=0.005 for superiority) co-primary endpoint of hospitalization for heart failure and CV death

 

NS

(HR=0.93, 95% CI: 0.84-1.03, p<0.001 for non-inferiority, p=0.17 for superiority)

co-primary endpoint of 3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=0.98, 95% CI: 0.82-1.17)

 

All-Cause: NS

(HR=0.93, 95% CI: 0.82-1.04)

Hospitalization for Heart Failure: 17% RRR

(HR=0.83, 95% CI: 0.73-0.95, p=0.005 for superiority)

VERTIS CV for ertugliflozin (Merck/Pfizer’s Steglatro) Completed – reported ADA 2020

8,246

99.9%

Age: 64

BMI: 31- 32

A1c: 8.2%

Diabetes Duration: 13 years

3.5 years

Yes – 76% on metformin, 47% on insulin, 41% on SUs, 11% on DPP-4s, 3% on GLP-1s

NS (HR=0.97; 95% CI: 0.85-1.11) 3-point MACE (CV death, nonfatal MI, nonfatal stroke)

CV death: NS (HR=0.92; 95% CI: 0.77-1.11; p=0.39)

Significant effect on HHF nonetheless – 30% RRR (HR=0.70; 95% CI: 0.54-0.90; p=0.006)

SCORED for sotagliflozin (Sanofi/Lexicon’s Zynquista)

Completed March 2021

 

Trial closed early due to COVID and funding issues

10,584

88%

Patients with T2D and CKD

Age: 69 years

BMI: 31.8

A1c: 8.3%

16 months

Yes – 88% on RAAS inhibitor, 55% on metformin, 27% on SUs, 20% on DPP-4s, 63% on insulin, 6% on GLP-1

26% RRR (HR=0.74; 95% CI: 0.63-0.88), p=0.0004, NNT=54)

(total CV death, HHF, and urgent HF visit)

CV death: NS (HR=0.90; 95% CI: 0.73-1.12)

 

All-cause mortality: NS (HR=0.99; 95% CI: 0.83-1.18)

HHF included in primary endpoint; only enrolling those w/ eGFR 25-60 mL/min/1.73 m2

GLP-1 Agonists

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

LEADER for liraglutide (Novo Nordisk’s Victoza) (outcomes paper)

Completed – reported ADA 2016

9,340

81%

Age: 64

BMI: 33

A1c: 8.7%

Diabetes Duration: 13 years

3.8 years

No other GLP-1 agonists or DPP-4 inhibitors

13% RRR

(HR=0.87, 95% CI: 0.78-0.97, p=0.01 for superiority, p<0.001 for non-inferiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: 22% RRR

(HR=0.78, 95% CI: 0.66-0.93)

All-Cause: 15% RRR

(HR=0.85, 95% CI: 0.74-0.97)

 

Indication for reducing MACE approved by FDA August 2017

Heart Failure: NS

(HR=0.87, 95% CI; 0.73-1.05)

REWIND for dulaglutide (Lilly’s Trulicity)

(outcomes paper) Completed – reported ADA 2019

9,901

31%

Age: 66

BMI: 32

A1c: 7.3%

Diabetes Duration: 10 years

5.4 years

No other GLP-1 agonists or DPP-4 inhibitors

12% RRR

(HR=0.88, 95% CI: 0.79-0.99, p=0.026 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=0.91, 95% CI: 0.78-1.06)

All-Cause: NS

(HR=0.90, 95% CI: 0.80-1.01)

No difference between primary and secondary prevention cohorts (HR=0.87, 95% CI: 0.74-1.02 for both)

EXSCEL for exenatide once-weekly (AZ’s Bydureon) (outcomes paper)

Completed – reported EASD 2017

14,752

73%

Age: 63

BMI: 32

A1c: 8.0%

Diabetes Duration: 12 years

3.2 years

No other GLP-1 agonists

NS

(HR=0.91, 95% CI: 0.83-1.00, p<0.001 for non-inferiority, p=0.06 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=0.88, 95% CI: 0.76-1.02)

All-Cause: exploratory

(HR=0.86, 95% CI: 0.77-0.97)

Heart Failure: NS

(HR=0.94, 95% CI: 0.78-1.13)

SUSTAIN-6 for semaglutide (Novo Nordiks’s Ozempic) (outcomes paper)

Completed – reported EASD 2016

3,297

83%

Age: 65

BMI: 33

A1c: 8.7%

Diabetes Duration: 14 years

2.1 years

No other GLP-1 agonists or DPP-4 inhibitors

26% RRR

(HR=0.74, 95% CI: 0.58-0.95, p=0.02 for superiority, p<0.001 for non-inferiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=0.98, 95% CI: 0.65-1.48)

All-Cause: NS

(HR=1.05, 95% CI: 0.74-1.50)

 

 

76% increased risk for retinopathy w/ semaglutide (HR=1.76, 95% CI: 1.11-2.78); Premarket CVOT not designed for superiority; does not support CV indication

Heart Failure: NS

(HR=1.11, 95% CI: 0.77-1.61)

ELIXA for lixisenatide (Sanofi’s Adlyxin) (outcomes paper)

Completed – reported ADA 2015

6,068

100%

Age: 60

BMI: 30

A1c: 7.7%

Diabetes Duration: 9 years

2.1 years

No other GLP-1 agonists or DPP-4 inhibitors

NS

(HR=1.02, 95% CI: 0.89-1.17, p=0.81)

4-point MACE (CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina)

 

CV: NS

(HR=0.98, 95% CI: 0.78-1.22)

All-Cause: NS

(HR=0.94, 95% CI: 0.78-1.13)

Heart Failure: NS

(HR=0.96, 95% CI: 0.75-1.23)

 

HARMONY for albiglutide (GSK’s Tanzeum)

(outcomes paper)

Completed – reported EASD 2018

9,463

100%

 

Age: 64

BMI: 32

A1c: 8.7%

Diabetes Duration: 14 years

1.6 years

No other GLP-1 agonists

22% RRR

(HR=0.78, 95% CI: 0.68-0.90, p=0.0006 for superiority, p<0.0001 for non-inferiority)

CV: NS

(HR=0.93, 95% CI: 0.73-1.19)

All-Cause: NS

(HR=0.95, 95% CI: 0.79-1.16)

GSK has withdrawn commercial support for Tanzeum; current commercial status unclear

PIONEER 6 for oral semaglutide (Novo Nordisk)

Topline results announced

3,183

85%

Age: 66

BMI: 32

A1c: 8.2%

Diabetes duration: 15 years

1.3 years

No other GLP-1 agonists or DPP-4 inhibitors

NS (HR=0.79, 95% CI: 0.57-1.11, p<0.001 for non-inferiority, p=0.17 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: 51% RRR

(HR=0.49, 95% CI: 0.27-0.92, p=0.03)

All-Cause: 49% RRR

(HR=0.51, 95% CI: 0.31-0.84, p=0.008)

 

AMPLITUDE-O for efpeglenatide (ex-Sanofi) (outcomes paper) completed.

Read out at ADA 2021

4,076

90%

Age: 64.5

BMI: 33

A1c: 8.9%

Diabetes duration: 15.4 years

1.8 years

Pre-randomization therapy continued, no DPP-4s or GLP-1s

27% RRR

(HR= 0.73; 95% CI: 0.58-0.92; p<0.0001 for non-inferiority; p=0.0069 for superiority) (first non-fatal MI, stroke, or death from CVD or undetermined cause)

Not reported

32% RRR in kidney composite outcome (HR=0.68; 95% CI: 0.57-0.79; p<0.0001) (decrease in eGFR of ≥40% for ≥30 days, ESKD or death from any cause)

SOUL for Novo Nordisk's oral semaglutide 

Ongoing – expected completion 2024

~9,642

 

-

-

-

-

-

SELECT – for semaglutide Ongoing –expected completion 2023

**does NOT include PWD, only people with obesity or overweight**

~17,500

 

-

-

-

-

-

DPP-4 Inhibitors

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

EXAMINE for alogliptin (Takeda’s Nesina) (outcomes paper)

Completed – reported ESC 2013

5,380

100%

Age: 61

BMI: 29

A1c: 8.0%

Diabetes Duration: 7 years

1.5 years

No other DPP-4 inhibitors or GLP-1 agonists

NS

(HR=0.96, 95% CI: 0.84-1.16)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=0.85, 95% CI: 0.66-1.10)

All-Cause: NS

(HR=0.88, 95% CI: 0.71-1.09)

 

Heart Failure: NS

(HR=1.07, 95% CI: 0.79-1.46)

 

SAVOR-TIMI for saxagliptin (AZ’s Onglyza) (outcomes paper)

Completed – reported ESC 2013

16,492

79%

Age: 65

BMI: 31

A1c: 8.0%

Diabetes Duration: 10 years

2.1 years

No other DPP-4 inhibitors or GLP-1 agonists

NS

(HR=1.00, 95% CI: 0.89-1.12, p<0.001 for non-inferiority, p=0.99 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=1.03, 95% CI: 0.87-1.22)

All-Cause: NS

(HR=1.11, 95% CI: 0.97-1.27)

 

Significant signal for increased risk of heart failure with saxagliptin

Heart Failure:  27% risk increase

(HR=1.27, 95% CI: 1.07-1.51)

TECOS for sitagliptin (Merck’s Januvia) (outcomes paper)

Completed – reported ADA 2015

14,671

100%

Age: 66

BMI: 30

A1c:7.2%

Diabetes Duration: 12 years

3.0 years

No other DPP-4 inhibitors or GLP-1 agonists, rosiglitazone prohibited at enrollment & discouraged during trial

NS

(HR=0.98, 95% CI: 0.89-1.08, p<0.001 for non-inferiority)

4-point MACE (CV death, non-fatal MI, non-fatal stroke, hospitalization or unstable angina)

CV: NS

(HR=1.03, 95% CI: 0.89-1.19)

All-Cause: NS

(HR=1.01, 95% CI: 0.90-1.14)

 

Heart Failure: NS

(HR=1.00, 95% CI: 0.83-1.20)

 

CARMELINA for linagliptin (Lilly’s Tradjenta)

Completed – reported EASD 2018

7,003

57% (100% CVD or CKD)

Age: 66

BMI: 31

A1c: 7.9%

Diabetes Duration: -

-

No DPP-4 inhibitors, GLP-1 agonists, or SGLT-2 inhibitors

NS

(HR=1.02, 95% CI: 0.89-1.17, p=0.0002 for non-inferiority, p=0.7398 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS 

(HR=0.96, 95% CI: 0.81-1.14)

All-Cause: NS

(HR=0.98, 95% CI: 0.84-1.13)

Albuminuria progression: HR=0.86, 95% CI: 0.78-0.95, p=0.0034

Heart failure: NS

(HR=0.90, 95% CI: 0.74-1.08)

CAROLINA for linagliptin vs. glimepiride

Ongoing – expected completion March 2019; internal readout in 2018

6,072

35%

Age: 64

BMI: 30

A1c: 7.2%

Diabetes Duration: 6 years

-

No history or baseline use of DPP-4 inhibitors, GLP-1 agonists, insulin (>2 weeks), TZDs

NS

(HR=0.98, 95% CI: 0.84-1.14)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS 

(HR=1.00, 95% CI: 0.81-1.24)

All-Cause: NS

(HR=0.91, 95% CI: 0.78-1.06)

Significantly lower risk on all hypoglycemia endpoints with linagliptin

Insulin

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

DEVOTE for insulin degludec (Novo Nordisk’s Tresiba) (outcomes paper)

Completed – reported ADA 2017

7,637

85%

Age: 65

BMI: 34

A1c: 8.4%

Diabetes Duration: 16 years

2 years

Any

NS

(HR=0.91, 95% CI: 0.78-1.06, p<0.001 for non-inferiority, p=0.21 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=0.96, 95% CI: 0.76-1.21)

All-Cause: NS

(HR=0.91, 95% CI: 0.76-1.11)

 

Severe hypoglycemia reduced by 40% with insulin degludec (HR=0.60, 95% CI: 0.48-0.76); nocturnal severe hypoglycemia reduced by 53% (HR=0.47, 95% CI: 0.31-0.73)

ORIGIN for insulin glargine (Sanofi’s Lantus) (outcomes paper)

Completed – reported ADA 2012

12,537

59%

Age: 64

BMI: 30

A1c: 6.4%

Diabetes Duration: 5 years

6.2 years

Any therapy besides Lantus

NS

(HR=1.02, 95% CI: 0.94-1.11, p=0.63 for superiority)

3-point MACE (CV death, non-fatal MI, non-fatal stroke)

CV: NS

(HR=1.00, 95% CI: 0.89-1.13)

All-Cause: NS

(HR=0.98, 95% CI: 0.90-1.08)

-

PCSK9 inhibitors

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

FOURIER for evolocumab (Amgen’s Repatha) (outcomes paper)

Completed – reported ACC 2017

27,564

100%

Age: 63

Weight: 85 kg (187 lbs)

2.2 years

High or moderate intensity statin therapy required

15% RRR

(HR=0.85, 95% CI: 0.79-0.92)

5-point MACE (CV death, non-fatal MI, non-fatal stroke, coronary revascularization, hospitalization for unstable angina)

CV: NS

(HR=1.05, 95% CI: 0.88-1.25)

All-Cause: NS

(HR=1.04, 95% CI: 0.91-1.19)

 

-

ODYSSEY Outcomes for alirocumab (Sanofi/Regeneron’s Praluent) (outcomes paper forthcoming)

Completed – reported ACC 2018

18,924

100%

Age: 58

Weight: -

2.8 years

High-intensity atorvastatin/rosuvastatin therapy required

15% RR

(HR=0.85, 95%CI: 0.78-0.93)

5-point MACE (CV death, non-fatal MI, non-fatal stroke, coronary revascularization, hospitalization for unstable angina)

CV: NS

(HR=0.88, 95% CI: 0.74-1.05)

All-Cause: 15% RRR (observational)

(HR=0.85, 95% CI: 0.73-0.98)

 

 

-

 

 

Multi-Agonists

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

SURPASS-CVOT  for tirzepatide Ongoing –estimated completion 2024

~12,500

-

-

-

-

-

Other

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Baseline Characteristics

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

FIGARO-DKD for finerenone (Bayer’s Kerendia) Completed – read out at ESC 2021

7,437

45%

Age: 64 years

A1c: 7.7%

eGFR:68 mL/min/1.73m2

Diabetes Duration:14.5 years

3.4 years

On guideline directed medical therapy (8% on SGLT-2, 7% on GLP-1)

13% RRR (HR=0.87, 95% CI: 0.76-0.98; P=0.03)

(CV death, non-fatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure)

CV death: NS (HR=0.90; 0.74-1.09)

All-Cause Mortality: NS (HR=0.89; 95% CI: 0.77-1.04)

Notably, non-significant finding on first secondary composite renal outcome (kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death) (in contrast to FIDELIO-DKD)

Heart Failure Outcomes Trials

SGLT-2 Inhibitors

Trial and Status

Enrollment

Baseline Characteristics

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

DAPA-HF for dapagliflozin (AZ’s Farxiga) (outcomes paper)

Completed – Read out at ESC 2019

4,744

Age: 66 years

BMI: 28

eGFR: 65 mL/min/1.73m2

45% had diabetes

18.2 months

Yes

26% RRR (HR=0.74; 95% CI: 0.65-0.85; p=0.00001; NNT=21)

3-point MACE (CV death/HF hospitalization/urgent HF visit)

CV death: 18% RRR (HR=0.82; 95% CI: 0.69-0.98; p=0.029)

All-cause mortality: 17% RRR (HR=0.83; 95% CI: 0.71=0.97)

Treatment effect was consistent across both patient populations of people with diabetes and people without diabetes

EMPEROR-Reduced for empagliflozin (Lilly/BI’s Jardiance) (outcomes paper) Completed – read out at ESC 2019

3,730

Age: 67 years

BMI: 28

eGFR: 62 mL/min/1.73m2

50% had diabetes

 

16 months

Yes

25% RRR (HR=0.75; 95% CI: 0.65-0.86; p<0.0001)

(death from cardiovascular causes/hospitalization for heart failure)

 

CV death: NS (HR=0.92; 95% CI: 0.75-1.12)

All-cause mortality: NS (HR=0.92; 95% CI: 0.77-1.10)

30% RRR on the key secondary endpoint of total HHFs (HR: 0.70; 95% CI: 0.58-0.85; p=0.0003)

No difference between patients with and without diabetes

SOLOIST-WHF for sotagliflozin (Sanofi/ Lexicon’s Zynquista) 

Completed March 2021

 

Trial closed early due to COVID and funding issues

1,222

 

Age: 70

BMI: 30-31

A1c: 7.1%

 

9 months

Yes – 91% on any RAAS inhibitor, 52% on metformin,

18% on SUs, 16% on DPP-4s, 35% on insulin

33% RRR (HR=0.67; 95% CI: 0.52-0.85; p=0. 0009, NNT=4) (total CV death, hospitalization for HF, and urgent HF visit)

Not reported

People treated with sotagliflozin were alive and out of hospital for 2.9 additional years per 100 patient years compared to placebo (p=0.027).

EMPEROR-Preserved for empagliflozin (Lilly/BI’s Jardiance) (outcomes paper) Completed – Read out at ESC 2021

5,988

Age: 72 years

BMI: 30

eGFR: 60.6 mL/min/1.73m2

49% had diabetes

26.2 months

Yes

21% RRR (HR=0.79; 0.69-0.90; p<0.001)

 

(CV death/HHF)

CV death: NS (HR=0.91; 95% CI: 0.76-1.09)

All-cause mortality: NS (HR=1.00; 95% CI: 0.87-1.15)

27% RRR on total heart failure hospitalizations (HR=0.73; 95% CI: 0.61-0.88; p<0.001)

DELIVER for dapagliflozin (AZ’s Farxiga)

Ongoing – expected completion 2022

~6,263

--

--

--

--

--

GLP-1 Receptor Agonists

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

STEP HFpEF for semaglutide Ongoing – expected completion 2023

~516

--

--

--

--

--

Multi Agonists

Trial and Status

Enrollment, Percent w/ Baseline CV Disease

Mean Age (years), BMI (kg/m2), A1c, and Diabetes Duration at Baseline

Study Design:

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

SUMMIT for tirzepatide Ongoing – expected completion 2023

~700

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Kidney Outcomes Trials

SGLT-2 Inhibitors

Trial and Status

Enrollment

Baseline Characteristics

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

CREDENCE for canagliflozin (J&J’s Invokana) Completed – Read out at WCN 2019

4,401

Age: 63

BMI: 31

A1c: 8.3

eGFR: 56 mL/min/1.73m2

Diabetes duration: 15.8 years

2.6 years

30% RRR (HR=0.70; 95% CI: 0.59=082; p=0.00001)

(end-stage kidney disease, doubling of the serum creatinine level, or renal or CV death)

CV death: NS (HR=0.78; 95% CI: 0.61-1.00; p=0.05)

 

All-cause mortality: NS  (HR=0.74; 95% CI: 0.63-0.86)

31% RRR in CV death or HHF (HR=0.69; 95% CI: 0.67 to 0.95; p=0.01)

34% RRR in end-stage kidney disease, doubling of serum creatinine, or renal death (HR=0.66; 95% CI: 0.53-0.81; p<0.001)

DAPA-CKD for dapagliflozin (AZ’s Farxiga) Completed (stopped early for overwhelming efficacy)– Read out at ESC 2020

4,304

Age: 62

BMI: 29.5

eGFR: 43 mL/min/1.73m2

67% with diabetes

2.4 years

Conducted on top of current CKD standard-of-care

39% RRR (HR=0.61; 95% CI: 0.51-0.72; p<0.001)

(sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes)

CV death: NS (HR=0.81, 95% CI: 0.58-1.12)

All-cause mortality: 31% RRR (HR=0.69; 95% CI: 0.53-0.88; p=0.004)

Primary endpoint was consistent for patients with and without diabetes interaction p-value: 0.24

EMPA-Kidney for empagliflozin Ongoing – expected completion 2022

~6,609

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GLP-1 Receptor Agonists

Trial and Status

Enrollment

Baseline Characteristics

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

FLOW for semaglutide Ongoing- expected completion 2024

~3,508

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Other

Trial and Status

Enrollment

Baseline Characteristics

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Mortality Results:

CV Death, All-Cause Mortality

Other Notable Findings

FIDELIO-DKD for finerenone (Bayer’s Kerendia) Completed – Read out at ASN 2020

~5,734

Age: 66

eGFR: 44 mL/min/1.73m2

Diabetes duration: 16.6 years

2.6 years

Yes – on guideline directed medical therapy (34% on ACE, 57% on diuretic, 74% on statin)

18% RRR (HR=0.82; 95% CI=0.73-0.93; p=0.0014; NNT=29)

(kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes)

CV death – not reported

All-cause mortality: NS (HR=0.90; 95% CI: 0.75-1.07; p=0.2348)

14% RRR for secondary CV endpoint (CV death, non-fatal MI, non-fatal stroke, or heart failure hospitalization) (HR=0.86, p=0.0339)

Obesity Outcomes Trials

Trial and Status

Comparator/Design

Enrollment

Mean Age (years), BMI (kg/m2), A1c

Median Follow Up, Concomitant Medications Allowed?

Primary Endpoint Result (components)

Other Notable Findings

STEP 1 for semaglutide -outcomes paper

Semaglutide 2.4 mg vs. placebo in people with obesity or overweight with complications

1,961

Age: 46

BMI: 37.9

A1c: 5.7%

*no patients with diabetes were enrolled in the study*

68 weeks

No other antiobesity medication within 90 days before enrollment

-14.9% body weight from baseline, -12.4% different than placebo (percentage change in body weight at week 68)

84.6% achieved a 5% of more reduction body weight

Change in body weight from baseline was -15.3 kg at week 68

-13.54 cm waist circumference with semaglutide compared to -4.13 with placebo

STEP 2 for semaglutide – outcomes paper

Semaglutide 2.4 mg vs. placebo and semaglutide 1.0 mg in people with type 2 diabetes and obesity or overweight with complications

1,210

Age:55

BMI: 35.7

A1c: 8.1%

68 weeks

No other antiobesity medication within 90 days before enrollment, no new investigational diabetes medications 90 days before screening

-9.6% change from baseline with semaglutide to 68 weeks in body weight vs -3.4% with placebo

 

69% of patients achieved weight reductions of at least 5% compared to 29% on placebo

N/A

STEP 3 for semaglutide – outcomes paper

Semaglutide 2.4 mg vs. placebo in people with obesity or overweight with complications, as an adjunct to intensive behavioral therapy

611

Age: 46

BMI: 38

A1c: 5.7%

*no patients with diabetes were enrolled in the study*

 

68 weeks

No other antiobesity medication within 90 days before enrollment

-16% change in body weight from baseline with semaglutide vs -5.7% with placebo

87% of participants achieved weight reductions of at least 5% compared to 48% of placebo

-8.3 cm waist circumference difference semaglutide vs placebo

STEP 4 for semaglutide – presented at ENDO 2021 (outcomes paper)

Continued semaglutide 2.4 mg treatment vs. withdrawal in people with obesity or overweight with complications

803

Age: 46

BMI: 38

A1c: 5.7%

68 weeks

No other antiobesity medication within 90 days before enrollment

7.9% reduction in body weight from randomization (week 20) to week 68 with semaglutide compared to +6.9% with placebo

-9.7 cm waist circumference difference semaglutide vs placebo

STEP 5 for semaglutide – presented at ObesityWeek 2021

Semaglutide 2.4 mg vs. placebo in people with overweight and obesity over 104 weeks.

304

Age: 47

BMI: 38.5

A1c: 5.7%

68 weeks

No other antiobesity medication within 90 days before enrollment

15.2% reduction in body weight with semaglutide at week 104 compared to 2.6% reduction with placebo

77% of participants lost more that 5% of their body weight compared to 34% with placebo

-9 cm waist circumference reduction with placebo

STEP 8 for semaglutide – presented at ObesityWeek 2021

Semaglutide 2.4 mg vs. liraglutide 3.0 gm in people with overweight or obesity

338

Age: 49

BMI: 37.5

A1c: 5.5%

68 weeks

No other antiobesity medication within 90 days before enrollment

15.8% weight loss from baseline of 231 lbs. vs. 6.4% on liraglutide vs. 1.9% on placebo

87% of participants on semaglutide achieved ≥5% body weight loss, compared to 58% on liraglutide and 30% on placebo

0.2% reduction in A1c with semaglutide compared to 0.1% increase on placebo

OASIS 1 for high dose semaglutide 50 mg

Ongoing – expected completion 2023

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~660

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SURMOUNT -1 for tirzepatide Ongoing – estimated completion 2024

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~2,539

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SURMOUNT-MMO for tirzepatide – announced at investor community meeting 2022

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