Summary Aims To evaluate in a real‐world setting the effectiveness and tolerability of available GLP‐1 RA drugs in patients with type 2 diabetes after a prolonged follow‐up. Materials and methods Observational, retrospective, single‐centre study in patients starting GLP‐1 RA therapy. Change in HbA1c, fasting plasma glucose (FPG) and body mass index (BMI) along with gastrointestinal (GI) adverse events and withdrawal from GLP‐1 RA therapy were evaluated. Lack of efficacy of GLP‐1 RA therapy according to prespecified goals was also measured. Results A total of 735 patients were included, mean age 59.7 years, duration of diabetes 9.01 years, HbA1c 8.18% and BMI 38.56 kg/m 2 . Average follow‐up was 18.97 months (range 4.2‐39.09). All HbA1c (0.93%; P < 0.01), FPG (24 mg/dL; P < 0.01) and BMI (1.55 kg/m 2 ; P < 0.05) were significantly reduced from baseline and maintained throughout follow‐up, regardless of prescribed GLP‐1 RA. GI adverse events were present in 13.81% of patients at first follow‐up visit, 37.07% of patients discontinued GLP‐1 RA treatment, and 38.63% did not meet efficacy goals. Conclusions In a real‐world setting, GLP‐1 RA therapy is largely prescribed in severely obese patients with a long‐standing and poorly controlled diabetes. All prescribed GLP‐1 RAs significantly decreased HbA1c, FPG and BMI. GI adverse events affected a low proportion of patients. Inversely, a high proportion of patients did not meet efficacy goals and/or discontinued GLP‐1 RA treatment. Baseline characteristics of patients and lack of adherence may represent important issues underlying differences in effectiveness in real‐world studies versus randomized trials.

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