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A similar trend was observed in studies of empagliflozin in combination with metformin, pioglitazone, and a sulfony-lurea.19,21,22,28 In the 104-week study of empagliflozin versus glimepiride, both as add-on to metformin, the proportion of patients achieving HbA1c PFKM 31%).20 However, the authors commented that significantly fewer patients received rescue therapy on empagliflozin (14.8%) than on glimepiride (23.7%; odds ratio, 0.530 [95% CI, 0.404, 0.696]; P (5�C10 pounds) were reported. Furthermore, imaging studies confirmed that 90% of the weight loss observed with empagliflozin was due to decreased fat mass, with reduction in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue.20 This is comparable to the weight loss observed with metformin or GLP-1 RAs of approximately BMS-754807 order 3 kg Selleck BLZ945 (6 pounds).43,44 As already mentioned, DPP-4 inhibitors are weight-neutral, while sulfonylureas, insulin, and thiazolidinediones are associated with weight gain. As effective therapies for weight loss are limited, clinicians recognize the value of additional weight loss from glucose-lowering agents. For example, although off-label, metformin has been used for weight loss,45 and the GLP-1 RA, liraglutide, was approved for use in chronic weight management.46,47 For obese patients motivated to lose weight, the combination of metformin, GLP-1 RA, and SGLT2 inhibitor is worth considering. In addition, as mentioned, adding empagliflozin in patients with T2DM who require insulin may help to offset insulin-associated weight gain. Patients with renal impairment Renal impairment is common in patients with T2DM.48 Patients with advanced renal impairment are a difficult-to-treat population due to the presence of associated comorbidities, reduced drug elimination, and an increased risk of hypoglycemia.49 Empagliflozin is contraindicated in patients with severe or end-stage renal disease (and would not be expected to have efficacy in these groups), but has been studied in patients with chronic kidney disease (CKD).28 In a 52-week study of patients with T2DM and stage 2, 3, or 4 CKD (defined as estimated glomerular filtration rate [eGFR] ��60 to