Chart 3.
Summary of findings and weight reduction in the tirzepatide SURPASS studies for treatment of type 2 diabetes mellitus and cardiovascular disease and SURMOUNT program for obesity.
| Study and findings | Changes in body weight | Changes in hemoglobin A1c | Safety and tolerability | References |
|---|---|---|---|---|
| SURPASS 1: Compared to placebo, tirzepatide 5, 10, and 15 mg SQ per week improved hemoglobin A1c and body weight among patients with type 2 diabetes mellitus. | Reduced body weight 8 to 11% in a dose-dependent manner, compared to a 1% body weight reduction with placebo in efficacy analysis set (Baseline BMI=31.9 kg/m2) | Reduced HbA1c 1.9% to 2.1% versus placebo in efficacy analysis set (Baseline HbA1c = 7.9%) | 14% discontinued study drug and 10% discontinued study prematurely (nausea, diarrhea, vomiting; no hypoglycemia). | [192] |
| SURPASS 2: Once a week tirzepatide (5 mg, 10 mg, or 15 mg) was superior to once-a-week subcutaneous semaglutide 1.0 mg in reducing HbA1c among patients with type 2 diabetes mellitus. | Reduced body weight 7.6–11.2 kg versus 5.7 kg body weight reduction with semaglutide (Baseline BMI = 34.2 kg/m2) | Reduced HbA1c 2.01–2.30% versus a reduction of 1.86% with semaglutide (Baseline HbA1c = 8.3%) | Side effects: nausea, diarrhea, decreased appetite and vomiting – similar percentages among the four treatment groups) | [193] |
| SURPASS 3: Tirzepatide was superior to titrated insulin degludec in reducing HbA1c, reducing body weight, and had a lower risk of hypoglycemia among patients with type 2 diabetes mellitus | Reduced body weight 7.5–12.9 kg compared to a 2.3 kg increase with degludec (estimated treatment difference range of 9.8 kg–15.2 kg). (Baseline BMI = 33.6 kg/m2) |
Reduced HbA1c 1.93–2.37% versus a reduction of 1.34% with degludec (Baseline HbA1c = 8.17%) | Tirzepatide had higher rates of nausea, diarrhea, decreased appetite and vomiting, but less hypoglycemia compared to degludec | [194] |
| SURPASS 4: Tirzepatide reduced HbA1c more than titrated inulin glargine and had a lower incidence of hypoglycemia among patients with type 2 diabetes and elevated cardiovascular risk. Open label 52 to 104-week study. | Reduced body weight 6.4–10.6 kg compared to 1.7 kg increase with insulin glargine (Baseline BMI = 33 kg/m2) | Reduced HbA1c by 2.24–2.58% compared to a reduction of 1.44% with insulin glargine (Baseline HbA1c = 8.5%) |
Adjudicated major adverse cardiac events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) were not increased with tirzepatide compared to insulin glargine. | [195] |
| SURPASS 5: Tirzepatide versus placebo added to titrated insulin glargine improved glycemic control among patients with type 2 diabetes. | Reduced body weight 5.4–8.8 kg compared to increase of 1.6 kg with placebo (Baseline BMI = 33.4 kg/m2) | Reduced HbA1c by 2.1–2.4% compared to a reduction of 0.9% with placebo (Baseline HbA1c = 8.31%) | Premature discontinuations of 10%–18% in a dose- dependent manner (5, 10, 15 mg per week), vs 3% in the placebo group. Most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%–21% vs 10%) and nausea (13%–18% vs 3%). | [196] |
| SURPASS 6: A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin | Study ongoing | Study ongoing | Study ongoing | [197] |
| SURPASS AP COMBO: A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea | Study ongoing (completed with no results yet reported) | Study ongoing (completed with no results yet reported) | Study ongoing (completed with no results yet reported) | [198] |
| SURPASS CVOT: A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes | Study ongoing | Study ongoing | Study ongoing | [199] |
| SURMOUNT-1: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight∗ | Study completed; publication pending∗ | Study completed; publication pending∗ | Study completed; publication pending∗ | [200] |
| SURMOUNT-2: A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight | Study ongoing | Study ongoing | Study ongoing | https://www.clinicaltrials.gov/ct2/show/NCT04657003 |
| SURMOUNT-3: A Study of Tirzepatide (LY3298176) In Participants After A Lifestyle Weight Loss Program | Study ongoing | Study ongoing | Study ongoing | https://www.clinicaltrials.gov/ct2/show/NCT04657016 |
| SURMOUNT-4: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss | Study ongoing | Study ongoing | Study ongoing | https://www.clinicaltrials.gov/ct2/show/NCT04660643 |
∗See Table 2 for preliminary efficacy findings of SURMOUNT-1.