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Natural history and management

Modern SUs such as GLIM and GLIC MR are associated with weight neutralizing/reducing effect compared to conventional SUs.[5] Furthermore, evidence suggests that GLIM may be the least in the class to endorse weight gain.[87,88] Nonetheless, weight gain associated with SUs may be due to improved utilization of consumed glucose and a subsequent reduction in glycosuria, thereby indicating reduction in glucotoxicity.[88] An extra increment in body weight has been observed when SUs were added to ongoing metformin therapy.[59] When compared to TZD, a pooled mean between-group difference of 0.9 kg (95% CI: 0.41.3 kg) favored the combination of metformin plus SU.[59] Similarly, the addition of pioglitazone was associated with more weight gain (2.5 kg) than GLIC (1.2 kg) in patients with metformin.[89] Several meta-analyses and RCTs reported that metformin-SU combination was associated with more weight gain compared to metformin-DPP-4I combinations and metformin-SGLT-2I combinations