Condition · High evidence

GLP-1s for T2D

GLP-1 receptor agonists (and the dual GLP-1/GIP tirzepatide) are first-line add-ons to metformin for adults with type 2 diabetes, with consistent HbA1c reduction and weight loss benefit.

Evidence

Across SURPASS-1 through SURPASS-5 (tirzepatide) and SUSTAIN-1 through SUSTAIN-10 (semaglutide), GLP-1/GIP therapies have produced HbA1c reductions of roughly 1.6–2.4 percentage points relative to placebo and 0.4–0.8 points relative to active comparators (insulin glargine, dulaglutide, semaglutide). Tirzepatide 15 mg outperformed semaglutide 1 mg in the head-to-head SURPASS-2 trial.

Where it sits in guidelines

The 2024 ADA Standards of Care recommend a GLP-1 receptor agonist (or tirzepatide) as a preferred second agent after metformin for adults with T2D and established cardiovascular disease, indicators of high CV risk, heart failure, or chronic kidney disease — independent of HbA1c level. Tirzepatide is increasingly used early when weight loss is a goal alongside glucose control.

What it doesn't do

GLP-1 therapies do not replace insulin in type 1 diabetes and are not appropriate as monotherapy in advanced beta-cell failure. They do not address the underlying autoimmune destruction in T1D.

Contraindications

  • Personal or family history of medullary thyroid carcinoma (MTC)
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • Pregnancy and breastfeeding