In Older Adults With Type 2 Diabetes, GLP-1 Receptor Agonists Decrease Major Adverse Cardiovascular Events; SGLT-2 Inhibitors Prevent Heart Failure Hospitalizations

Which treatments for type 2 diabetes improve outcomes in older adults?

In the network meta-analysis, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors improved patient-centered outcomes in older adults with type 2 diabetes but with differing effects on cardiovascular and renal outcomes. (Level of Evidence = 1a–)

The authors searched several databases and registries to identify randomized trials that compared drugs used to treat type 2 diabetes with placebo or other active medications in adults 65 years or older. The studies had to report patient-centered outcomes to be included. In addition to evaluating multiple individual outcomes, the authors also created composites for major adverse cardiac events (3-point composite: nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and renal outcomes (40% decrease in estimated glomerular filtration rate, end-stage renal disease, or renal death). They pooled data and conducted a network meta-analysis.

The authors included 22 trials (41,654 patients) that evaluated SGLT-2 inhibitors, GLP-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, metformin, sulfonylureas, and acarbose. None of the studies assessed neuropathy or retinopathy, and only one assessed cognitive function. Overall, the studies were at low or moderate risk of bias, and the authors found no evidence for publication bias. The authors did not report data in a manner conducive to estimating the number needed to treat (NNT) for the overall results, but they do report the NNTs for age groups (ie, 65 to 74 years and 75 years or older).

For cardiovascular events, either individually or the composite, only the GLP-1 receptor agonists significantly decreased the risk (overall relative risk [RR] = 0.83; 95% CI, 0.71–0.97; age group NNTs = 39 and 15, respectively). SGLT-2 inhibitors decreased hospitalizations for heart failure (overall RR = 0.66; 95% CI, 0.57–0.77; age group NNTs = 73 and 37, respectively). SGLT-2 inhibitors also decreased the renal composite (overall RR = 0.69; 95% CI, 0.53–0.89; age group NNTs = 86 and 71, respectively) and individual renal events. Although not nearly as clinically important, all the agents were more effective than placebo in various markers of glycemic control. More important, the sulfonylureas were the only class that increased weight and caused more hypoglycemia compared with placebo.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Reference: Pan SY, Su EL, Huang CJ, et al. Evaluation of glucose-lowering medications in older people: a comprehensive systematic review and network meta-analysis of randomized controlled trials. Age Ageing. 2024;53(8):afae175.