Table 2.
Summary of evidence on T2DM prevention with medications promoting both glucose-lowering and weight-loss.
| Study (year) | Eligibility | Number of Subjects | Interventions | Results | Mean or Median Follow up in years | Comments |
|---|---|---|---|---|---|---|
| A) Glucagon-like peptide-1 agonists | ||||||
| Rosenstock, et al. (2014) (30) | Obese, subjects, Mean BMI: 39.6 kg/m2 and IGT or IFG | 152 | Placebo vs Exenatide plus LSM | IGT or IFG normalized at end point in 77% of exenatide vs 56% of placebo subjects. | 24 weeks | |
| Le Roux et al. (2017) (31) | Prediabetes plus BMI of at least 30 kg/m2 or 27 kg/m2 with comorbidities. | 2254 | Once-daily subcutaneous liraglutide 3·0 mg or matched placebo plus LSM | In the liraglutide group 26 individuals (2%) of 1472 were diagnosed with T2DM vs 46 (6%) of 738 in the placebo group. The time to onset of T2DM over 160 weeks among all randomized individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001) |
160 weeks | |
| Garvey, et al. (2022) (32) Wilding, et al. (2021) (33) - STEP 1 |
BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related complication, excluding T2DM | 1961 | Once a week 2.4mg semaglutide vs placebo | Risk scores decreased from 18% to 7% with semaglutide, and 18% to 16% with placebo (61% vs. 13% reduction [p<0.01] | 68 weeks | 10-yr T2D risk was calculated post hoc, from STEP 1 (68 weeks) and STEP 4 (20-wk run-in on semaglutide, 48-wk randomized withdrawal) |
| Garvey, et al. (2022) (32) Rubino, et al. (2021) (34)- STEP 4 |
BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related complication, excluding T2DM | 902 | Once a week 2.4mg semaglutide vs placebo | Risk score reduction with semaglutide occurred during wks 0-20, from 21% to 8% but increased to 15% with switch to placebo (32% reduction vs. 41% increase [p<0.01] | 20-wk run-in on sema, 48-wk randomized withdrawal | As above |
| B) Tirzepatide | ||||||
| SURMOUNT-1 (35) | BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related complication, excluding T2DM | At baseline, 40.6% (n=1032 out of 2539) of subjects had prediabetes | Tirzepatide (5 mg, 10 mg, or 15 mg) or placebo | 95.3% of the participants with prediabetes at baseline in the treatment groups had reverted to normoglycemia, as compared with 61.9% of participants in the placebo group. | 1.4 | |
BMI, body-mass index; LSM, lifestyle modifications; IGT, impaired glucose tolerance; IFG, impaired fasting glucose; GDM, gestational diabetes mellitus; T2DM, type 2 diabetes mellitus; STEP, Semaglutide Treatment Effect in People with Obesity; SURMOUNT: Efficacy and safety of Tirzepatide once weekly in participants without type 2 diabetes who have obesity or are overweight with weight- related comorbidities.