Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial

Abstract

Context

Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin.

Objective

To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D.

Design

Phase 3a, double-blind, placebo-controlled, 30-week trial.

Setting

This study included 90 sites in five countries.

Patients

We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.

Interventions

Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.

Main Outcome Measures

Primary endpoint was change in glycated Hb (HbA _1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30.

Results

At week 30, mean HbA _1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, –1.35 (14.8 mmol/mol); 95% CI, –1.61 to –1.10 and ETD, –1.75% (19.2 mmol/mol); 95% CI, –2.01 to –1.50; both P < 0.0001]. Severe or blood glucose–confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, –2.31; 95% CI, –3.33 to –1.29 and ETD, –5.06; 95% CI, –6.08 to –4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders.

Conclusions

Semaglutide, added to basal insulin, significantly reduced HbA _1c and body weight in patients with uncontrolled T2D vs placebo.

Abstract

The randomized, double-blind SUSTAIN 5 trial demonstrated the superiority of once-weekly semaglutide vs placebo in patients with uncontrolled T2D on basal insulin therapy.