Are Circulating Mg2+ Levels Associated with Glucose Tolerance Profiles and Incident Type 2 Diabetes?

Magnesium (Mg2+) is an enzyme co-factor that plays a key role in many biochemical reactions, as well as in glucose metabolism. Clinical evidences have demonstrated that depletion of serum Mg2+ increases exponentially with the duration of type 2 diabetes mellitus (T2DM). Diabetes is associated with low Mg2+, and hypomagnesemia is associated with insulin resistance, inflammation, and increased risk for cardiovascular disease. In subjects at high risk of inflammation and insulin resistance, supplementation of Mg2+ alone ameliorates both phenotypes, slowing the development and progression of hepatic steatosis. We analyze the relationship between serum Mg2+ levels and the onset of T2DM in a large cohort of well-characterized adult white individuals participating in the CATAMERI study, who were reexamined after a mean follow-up of 5.6 ± 0.9 years. In our analysis we acquired a significant negative correlation between Mg2+ levels, fasting glucose, and 2h-post load glucose in subjects who underwent an OGTT. Moreover, Mg2+ levels correlated negatively with fasting insulin levels, and positively with the lipid profile. As for the detrimental effect of lower circulating Mg2+ levels, our data revealed a significant reduction of T2DM risk of about 20% for each 1 mg/dL increase of circulating Mg2+. The present results are consistent with the theory that Mg2+ supplementation could ameliorate insulin sensitivity reducing the risk to develop T2DM.

[Effects of anti-diabetic therapy on overweight/obesity and dyslipidemia: traditional hypoglycemic agents (metformin, sulfonylureas, thiazolidinediones) versus glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors]. / Effetti della terapia del diabete su sovrappeso/obesità e dislipidemia: terapie tradizionali (metformina, sulfaniluree, tiazolidinedioni) versus analoghi del glucagon-like peptide-1 e inibitori della dipeptidil peptidasi-4.

Obesity and dyslipidemia often coexist in patients with type 2 diabetes and contribute to increase the risk of cardiovascular events. Pharmacological treatments of diabetes often result in weight gain, an undesirable event associated with a worse cardiovascular risk profile and decreased adherence to therapy. Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs have been shown to improve glycemic control without promoting weight gain and to exert beneficial effects on lipid profile by reducing total and LDL cholesterol, triglycerides, and free fatty acid levels. DPP-4 inhibitors have demonstrated to be weight neutral whereas treatment with GLP-1 analogs is associated with a significant weight loss. DPP-4 and GLP-1 analogs represent a new therapeutic option for type 2 diabetes, which offers the advantage of combining glycemic control with beneficial effects on body weight and lipid profile, thus providing greater cardiovascular protection.

A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus.

BACKGROUND: Liraglutide, a human glucagon-like peptide 1 (GLP-1) analogue that has received marketing approval from the European Commission, is a treatment for type 2 diabetes mellitus (DM) that is administered as a once-daily subcutaneous injection. OBJECTIVE: The aim of this review was to summarize the efficacy and safety data published about liraglutide, focusing on data from Phase III clinical trials. METHODS: Relevant English-language publications were identified through a search of MEDLINE and EMBASE (from 1948 to October 2009). The search terms included the following: GLP-1, incretin effect, liraglutide, NN2211, exenatide, sitagliptin, and vildagliptin. Original research papers about liraglutide that were published in peer-reviewed journals were considered. RESULTS: The literature search identified 39 relevant publications. The efficacy and tolerability of oncedaily liraglutide at doses of 0.6, 1.2, and 1.8 mg for type 2 DM, in combination with, and compared with, other type 2 DM treatments were investigated in the Liraglutide Effect and Action in Diabetes (LEAD) Phase III clinical trial program. In the LEAD studies, consistent reductions in glycosylated hemoglobin (HbA(1c)) of up to 1.6% were seen with liraglutide, and up to 66% of patients achieved the HbA(1c) goal of <7%. Fasting and postprandial plasma glucose levels were also consistently reduced across the LEAD trials by up to 43 mg/dL (2.4 mmol/L) and 49 mg/dL (2.7 mmol/L), respectively. Hypoglycemia was reported at a rate of 0.03 to 1.9 events per patient annually. Liraglutide significantly improved beta-cell function, as measured by homeostasis model assessment for beta-cell function analysis (20%-44%) and by ratios of pro-insulin to insulin (-0.11 to 0.01). Consistent reductions in systolic blood pressure up to 6.7 mm Hg were also observed for liraglutide treatment. Liraglutide treatment, as monotherapy and in combination with oral antidiabetic drugs (OADs), was associated with weight loss of up to 3.24 kg. Overall, liraglutide was well tolerated. Nausea was the most common adverse event observed with liraglutide treatment, reported by 5% to 29% of patients; however, nausea was generally mild and transient. CONCLUSION: Once-daily liraglutide was effective and well tolerated when used as monotherapy or in combination with OADs in patients with type 2 DM, and is therefore a promising new treatment option for the management of type 2 DM.