Pair page — what's published on the two together
Insulin with Semaglutide
Studied together in large type 2 diabetes trials: semaglutide added to basal insulin, and IcoSema, a weekly insulin-plus-semaglutide injection.
The receipt
3 studies gave them to people together
Controlled trials · Phase 3 trials in type 2 diabetes
- Evidence on the combination
- Controlled trials
Rodbard et al., 2018 · Mathieu et al., 2025 · Billings et al., 2025
What each does alone
- Libido & hormones · Daily shotInsulinHormone8 million Americans need it for diabetes; some bodybuilders inject it for size. Misuse can kill.Approved drugFDA approvedHypoglycemia can be fatalChecked Oct 18
- Weight loss · Weekly shotSemaglutideGLP-1The weekly shot the FDA approved as Ozempic and Wegovy. Weight loss in its main trial: 14.9%, on average.Approved drugFDA approvedChecked Oct 18
Mechanism overlap · reasoning, not evidence
- Insulin
- Hormone — Pancreatic Peptide Hormone
- Semaglutide
- GLP-1 Receptor Agonist — Metabolic
Reasoning, not evidence: what each is described to do says nothing about what they do together.
What the studies found
SUSTAIN 5, semaglutide added to basal insulin (Rodbard et al., 2018)
- What was given — 397 adults with uncontrolled type 2 diabetes on basal insulin, with semaglutide 0.5 or 1.0 mg weekly or placebo added for 30 weeks.
- What it found — HbA1c fell 1.4 and 1.8 points vs 0.1 on placebo; weight fell 3.7 and 6.4 kg vs 1.4 kg. Stopping for adverse events: 4.5% and 6.1% vs 0.8%, mainly gastrointestinal.
COMBINE 1, IcoSema vs insulin icodec (Mathieu et al., 2025)
- What was given — 1,291 adults on daily basal insulin, randomized to weekly IcoSema (insulin icodec and semaglutide in one injection) or insulin icodec alone, for 52 weeks.
- What it found — HbA1c fell 1.55 vs 0.89 points. Clinically significant or severe hypoglycaemia: 0.14 vs 0.63 episodes per person-year.
- Limits — Open label; funded by Novo Nordisk.
COMBINE 3, IcoSema vs basal-bolus insulin (Billings et al., 2025)
- What was given — 679 adults on daily basal insulin, randomized to weekly IcoSema or basal-bolus insulin (daily glargine plus two to four daily aspart injections), for 52 weeks.
- What it found — HbA1c fell 1.47 vs 1.40 points (non-inferior). Weight differed by −6.72 kg in IcoSema's favour; hypoglycaemia 0.21 vs 2.23 episodes per person-year.
- Limits — Open label; funded by Novo Nordisk.
Every trial here was in type 2 diabetes.
Legal Status
Insulin: FDA approved. Prescribed by a doctor, made by a manufacturer.
Semaglutide: FDA approved. Prescribed by a doctor, made by a manufacturer.
References
- Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, et al. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial. J Clin Endocrinol Metab. 2018;103(6):2291-2301. PMID: 29688502.
- Mathieu C, Giorgino F, Kim SG, Larsen JH, Philis-Tsimikas A, Ramachandran A, et al. Once-weekly IcoSema versus once-weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open-label, multicentre, treat-to-target, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2025;13(7):568-579. PMID: 40482671.
- Billings LK, Andreozzi F, Frederiksen M, Gourdy P, Gowda A, Ji L, et al. Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2025;13(7):556-567. PMID: 40482670.
Checked 14 Oct 2026 | A literature lookup, not a recommendation to combine anything.