glucagon-like-peptide-1 and Diabetic-Foot

To compare the contribution of sodium-glucose cotransporter-2 inhibitors (SGLT2is) with that of DPP4i or GLP-1ra toward lower extremity amputation rate.. Electronic databases were searched for articles published on the differences between the rates of lower extremity amputation among patients with type 2 diabetes mellitus (T2DM) undergoing SGLT2i treatment and those undergoing other anti-hyperglycemic agent (dipeptidyl peptidase-4 inhibitors [DPP4is], glucagon-like peptide-1 receptor agonist [GLP-1as], or sulfonylurea [SUs]) treatments. Random-effect models were used to generate data if heterogeneity was detected.. Eight studies based on retrospective case-control designs with propensity matching were included. The propensity score-matching method increased credibility. Compared with SGLT2i treatment, DPP4i or GLP-1a treatment tended to result in a higher amputation rate (pooled hazard ratio [HR] = 1.1, 95% confidence interval [CI]: 0.98-1.23), whereas SU treatment resulted in similar amputation rates (pooled HR = 0.92, 95% CI: 0.74-1.13). After excluding the heterogeneous study, the meta-analysis of the remaining studies attained a statistical value (pooled HR = 0.81, 95% CI: 0.65-1.01).. The study findings suggest that, with respect to diabetic foot-related limb amputations, SGLT2is are not superior to novel anti-hyperglycemic agents (DPP4is and GLP-1as) or other types of oral hypoglycemic agents (SUs). Therefore, SGLT2is may not have significantly positive effects on the prognosis for T2DM patients with complicated diabetic foot.

Topics: Amputation, Surgical; Diabetes Mellitus, Type 2; Diabetic Foot; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Extremities; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors

The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, both micro- and macroangiopathy strongly contribute to the development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. With adequate treatment, some ulcers may last only weeks; however, many ulcers are difficult to treat and may last months, in certain cases years; 19-35% of ulcers are reported as nonhealing. As no efficient therapy is available, it is a high priority to develop new strategies for treatment of this devastating complication. Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. Although elucidation of the pathophysiologic importance of these aspects awaits further confirmations, the present study evidences an additional aspect of how DPP-4 inhibition might contribute to improved ulcer outcome.

Topics: Adamantane; Aged; Aged, 80 and over; Capillaries; Chronic Disease; Diabetes Mellitus, Type 2; Diabetic Foot; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Female; Gene Expression Regulation; Glucagon-Like Peptide 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Italy; Male; Middle Aged; Neovascularization, Physiologic; Nitriles; Oxidative Stress; Proteasome Endopeptidase Complex; Pyrrolidines; RNA, Messenger; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A; Vildagliptin; Wound Healing