SGLT2 inhibitor–GLP-1 agonist combo improves outcomes in patients with T2DM or obesity

Use of combination therapy with sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for treating type 2 diabetes mellitus (T2DM) or obese patients yields favourable effects on glycaemic control, body weight and systolic blood pressure (SBP) without increasing the incidence of adverse events, according to the results of a meta-analysis.

Researchers accessed multiple databases to search for trials that compared the efficacy and safety of co-initiation of SGLT2 inhibitors and GLP-1 agonists with monotherapy, placebo, or other antihyperglycaemic agents over a follow-up of at least 16 weeks in a population of adults with T2DM or obesity.

The search yielded five randomized controlled trials (RCTs) and six non-RCTs involving 1,604 participants (mean age range, 53.40–61.02 years). The mean length of diabetes ranged from 7.37 to 14.85 years, while the follow-up time ranged from 18 to 52 weeks. Four SGLT2 inhibitors were evaluated: canagliflozin, dapagliflozin, empagliflozin and ipragliflozin. Four GLP-1 agonists were evaluated as combination treatment: dulaglutide, exenatide, liraglutide and lixisenatide.

Pooled data showed that relative to control/placebo, the combination therapy group significantly reduced fasting plasma glucose level by 1.28 mmol/L (p<0.001), 2-h postprandial glucose by 1.34 mmol/L (p<0.001) and glycosylated haemoglobin by 1.32 percent (p<0.001).

The combination treatment also produced decreases in body weight (–0.93 kg; p<0.001) and SBP (–1.05 mm Hg; p<0.001).

There were no significant between-group differences observed in the incidence of genital mycotic infections (relative risk [RR], 1.67; p=0.651) and urinary infections (RR, 1.25; p=0.905).

The combination vs control therapy led to a decreased incidence of cardiovascular events (RR, 0.19; p=0.403) but a higher incidence of hypoglycaemia (RR, 2.22; p=0.71).