Tirzepatide, taken once a week at 5, 10, or 15 mg, leads to big drops in weight (about 10–15 kg) and improves blood sugar control in people with type‑2 diabetes or obesity. The higher the dose, the bigger the benefit. It appears safer than insulin for serious side‑effects and low blood sugar, but it can cause more stomach upset.

Tirzepatide has shown benefits in weight reduction and glycemic control in type 2 diabetes and obesity, but its relative efficacy and safety across doses remain unclear. We conducted a PROSPERO-registered systematic review and network meta-analysis of randomized controlled trials up to July 2024. Trials comparing tirzepatide (5, 10, or 15&#x2009;mg weekly) with placebo, insulin, or GLP-1 receptor agonists in adults with type 2 diabetes and/or obesity were included. Random-effects models estimated mean differences (MDs) or relative risks (RRs), with treatment ranking assessed by SUCRA and evidence certainty rated with CINeMA. Thirteen RCTs (14,007 participants) were included. Tirzepatide produced dose-dependent weight reductions versus insulin (MD -14.5&#x2009;kg for 15&#x2009;mg; -12.5&#x2009;kg for 10&#x2009;mg; -10.2&#x2009;kg for 5&#x2009;mg; all <i>p</i> &lt;&#x2009;0.0001). The likelihood of &#x2265;15% weight loss (RR 4.83 for 15&#x2009;mg), HbA1c reduction (MD -12.6&#x2009;mmol/mol), and normoglycemia (RR 11.3) was significantly higher with tirzepatide. Safety analyses showed fewer serious adverse events (RR 0.71-0.77) and hypoglycemia (RR 0.44-0.50) than insulin, but more gastrointestinal events. Tirzepatide provides superior weight loss, glycemic improvements, and favorable safety versus insulin and other comparators, supporting its role as a leading therapy for type 2 diabetes and obesity.