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BackgroundLaparoscopic sleeve gastrectomy is an effective metabolic surgery; however, some patients experience weight regain and worsening of type 2 diabetes mellitus (T2DM) over the long term. Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated potent weight loss and glucose-lowering effects. This study evaluated the clinical outcomes of TZP treatment in patients facing weight regain and insufficient glycemic control after LSG.Methods and resultsWe performed a retrospective clinical analysis of three male patients with obesity-associated T2DM who developed significant weight regain and suboptimal glycemic control several years after undergoing LSG. Despite repeated nutritional counseling and behavioral modification, their conditions remained refractory. Following the initiation of weekly TZP treatment, all three patients achieved substantial weight reduction and significant improvements in HbA1c levels. Specifically, Case 1 achieved a total weight loss (%TWL) of 14.0% from the pre-LSG baseline (13.2% weight loss specifically from TZP initiation) over 12 months. Case 2 achieved a %TWL of 13.2% from the pre-LSG baseline (8.5% weight loss from TZP initiation) over 6 months. Case 3 achieved a %TWL of 27.3% from the pre-LSG baseline (28.7% weight loss from TZP initiation) over 9 months. Notably, all patients reached HbA1c levels below 6.0% (range: 5.2%–5.6%), surpassing the glycemic control achieved in the immediate postoperative period. TZP was well-tolerated, with only mild constipation reported as an adverse event.ConclusionTZP may serve as a promising therapeutic option for managing weight regain and insufficient glycemic control in patients after metabolic bariatric surgery, potentially delaying or eliminating the need for complex revisional surgery.