The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxagliptin has a very favourable side effect profile and may have other beneficial non-glycemic effects. The authors review the current available evidence for the safety, efficacy and saxagliptin’s place in therapy for type 2 diabetes mellitus. As understanding of the incretin hormones (GLP-1, GIP) expand we may see additional important non-glycemic effects that may affect the chronic management of type 2 diabetes mellitus.
The prevalence of obesity is increasing and is co-epidemic with type 2 diabetes mellitus (T2DM). Treatment of obesity has been less than adequate, particularly when managing morbidly obese patients. Research on T2DM has shown a number of new pharmacologic therapies along with the rapid employment of bariatric surgery. Improvement of T2DM, including its remission, after bariatric surgery has been recognized for more than a decade. However, not all procedures are the same. Restrictive procedures, malabsorptive procedures, or a combination of both procedures have their own categorical risks and benefits. Which procedure to choose has to do with many patient selection factors, notwithstanding insurance coverage. Based on operative and postoperative mortality data, laparoscopically assisted gastric bypass (LAGB) has been shown to be the safest bariatric surgery procedure. However, the Roux-en-Y gastric bypass procedure is one of the most widely used for obese patients with T2DM. The mechanisms involved in weight loss and improved blood glucose control appear to involve increased insulin sensitivity, decreased lipotoxicity/inflammation, and changes in gut hormones/incretins. The safety of bariatric procedures has improved; complication rates are low and mortality is < 1% for all procedures. As a result of the dramatic, positive impact of bariatric procedures on T2DM in obese patients, physicians should be cautious during patient selection to avoid performing the procedure on patients who are overzealous about reported outcomes, but who are not candidates for the procedure. Other data gaps still exist regarding diabetes surgery, which must be filled using data from well-designed, well-implemented randomized controlled clinical trials. In the future, it will be prudent to compare surgical interventions with other rigorous medical interventions in more robust studies. A combination of surgical, medical, and behavioral interventions should be considered for treating obese patients with T2DM.
Saxagliptin, a DPP-4 inhibitor, is one of an important new class of compounds, which seems to be particularly safe and effective especially in early treatment of T2DM.
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