Combining glucagon-like peptide 1 analogues with sodium-glucose cotransporter 2 inhibitors to treat patients with type 1 diabetes, BMI > 25 kg/m

Aims: We investigated the safety and efficacy of combining glucagon-like peptide-1 (GLP-1) analogues with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 1 diabetes, BMI > 25 kg/m ², and early chronic kidney disease. Methods: This single-centre pilot study (NCT05390307) randomised 60 participants to usual care, GLP-1, SGLT2i, GLP-1 + SGLT2i, or GLP-1 + SGLT2i + lifestyle modification for 6 months. The primary endpoint was change in bodyweight. Secondary endpoints included markers of kidney disease, glycaemic, blood pressure, and lipids. Analyses were performed using both intention-to-treat and per-protocol approaches. Results: In the intention-to-treat analysis, the GLP-1 + SGLT2i + lifestyle group achieved significantly greater bodyweight loss than usual care [-9·6%, (95 %CI −14·4, −4·9), p < 0.001], and SGLT2i alone [-8·0 (95 %CI −12·6, −3·4), p = 0·002]. No significant differences in glycaemia or blood pressure were observed among groups. However, the GLP-1 + SGLT2i + lifestyle showed a reduction in urine albumin creatinine ratio from 784·9mg/g (95 %CI 500·7, 1069·1) to 287·6mg/g (95 %CI −1·6, 576·8), p < 0·001). Adverse events occurred in 50% of participants in both the usual care (n = 6/12) and medication groups (n = 24/48). Conclusions: In patients with type 1 diabetes, BMI > 25 kg/m ², and chronic kidney disease, the combining GLP-1 + SGLT2i + lifestyle modification was safe and produced significant weight loss but did not significantly improve metabolic and blood pressure control.