Tirzepatide plus testosterone and training tied to muscle and grip gains in 93-man case series

A retrospective case series of 93 men treated at a single outpatient clinic reports that weekly tirzepatide combined with intramuscular testosterone cypionate and coaching focused on resistance exercise and protein intake was accompanied by large weight and fat loss, along with gains in estimated skeletal muscle mass and grip strength over 12 months ^[1].

The study, published in the journal Obesity Pillars, enrolled men with obesity and symptoms of testosterone deficiency whose morning total testosterone was below 400 ng/dL. Forty-five of the men had type 2 diabetes and 48 did not ^[1]. Body composition was measured with multifrequency bioelectrical impedance analysis, and grip strength with a dynamometer, at the start of the program and again at 3, 6 and 12 months. Blood work included HbA1c, high-sensitivity C-reactive protein, LDL cholesterol and trough total testosterone, and participants filled out the PROMIS Global Health 10 questionnaire ^[1].

Over the 12 months, body weight fell by 20.9 to 22.6 kilograms, or 18% to 20%, and fat mass fell by 16.6 to 17.1 kilograms, or 38% to 40% ^[1]. Lean body mass decreased by 4.0 to 6.1 kilograms. At the same time, bioelectrical-impedance-derived skeletal muscle mass rose by 1.6 to 3.7 kilograms, or 4% to 12%, and grip strength rose by 5.7 to 7.1 kilograms, or 18% to 21% ^[1].

Among the men with type 2 diabetes, HbA1c dropped from 10.1% to 5.8%. LDL cholesterol fell 20%, hs-CRP fell 43% to 53%, and physical and mental health PROMIS scores improved by 13% to 16% ^[1].

Doses of tirzepatide or testosterone were not reported, and the study does not describe side effects or how many participants dropped out. Follow-up beyond 12 months is not included.

Why it matters for patients

A common worry about GLP-1 and dual GLP-1/GIP weight-loss drugs is that some of the weight lost will be muscle. This case series does not settle whether tirzepatide on its own preserves or builds muscle. Every participant received the same package: tirzepatide, testosterone injections, and coaching on resistance training and protein intake ^[1].

That matters because the muscle and grip-strength numbers are the part of this study most often repeated online, and the testosterone is the part most often left out. Testosterone therapy is a prescription treatment with its own effects on muscle, so a gain in skeletal muscle mass in men receiving both drugs cannot be traced to either one ^[1]. The authors say so directly: "The uncontrolled multimodal design precludes attribution of these findings to individual components" ^[1].

The results also come from a narrow group. All participants were men with obesity and low morning testosterone plus symptoms of deficiency, and all were treated at one clinic, so the findings may not describe women, men with normal testosterone, or people using tirzepatide without testosterone ^[1].

One detail is easy to misread. Total lean body mass went down while the estimate of skeletal muscle mass went up. The authors suggest this pattern likely reflects a larger loss of non-muscle lean tissue than of muscle, not a gain in every kind of lean tissue ^[1].

What happens next

No randomized trial that separates the effects of tirzepatide, testosterone therapy and exercise has been reported. The paper appears in the September 2026 issue of Obesity Pillars, Volume 19 ^[1].