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Moreno J.L.,Manchester College
The Annals of pharmacotherapy

To evaluate the potential role of exenatide for weight loss in overweight or obese adults without diabetes. PubMed (1946-August 2012) and EMBASE (1974-August 2012) were used to conduct a literature search utilizing the terms exenatide, weight loss, obesity, and overweight. Additional references were identified by bibliographic review of relevant articles. Studies assessing the use of exenatide in adult subjects without type 2 diabetes or polycystic ovary syndrome and reporting effects on body weight were included. Five studies were identified that reported use of exenatide in nondiabetic adults and included weight change as an outcomes measure. In all 5 of these studies, subjects taking exenatide experienced statistically significant weight loss, which ranged from 2.0 ± 2.8 to 5.1 ± 0.5 kg. Two of the trials were randomized, placebo-controlled studies; 1 trial was a randomized, open-label investigation; 1 study had a prospective, open-label cohort design; and the remaining study was a chart review. Adverse events experienced with exenatide were primarily gastrointestinal in nature, although each trial reported the drug to be well tolerated. Obesity continues to be a national epidemic, while choices for effective pharmacologic treatments are extremely limited. Exenatide appears to have promising effects on weight in overweight or obese adults without type 2 diabetes. Further investigations with large, placebo-controlled trials assessing long-term weight loss as a primary outcome are warranted. Source

Vasilakou D.,Aristotle University of Thessaloniki | Karagiannis T.,Aristotle University of Thessaloniki | Athanasiadou E.,Aristotle University of Thessaloniki | Mainou M.,Aristotle University of Thessaloniki | And 5 more authors.
Annals of Internal Medicine

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs. Purpose: To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes. Data Sources: MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature. Study Selection: Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes. Data Extraction: Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Data Synthesis: Sodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n=11 232) and with active comparators in 13 studies (n=5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control. Limitation: Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods. Conclusion: Sodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear. © 2013 American College of Physicians. Source

There are number of means of methods to alter body composition, and metabolic issues, available for the adult who is overfat. The following is a systematic review and meta-analysis focused on comparing changes from treatment program for adults who are overfat based on analysis of aggregated effect size (ES) of inducing changes. So as to determine the relative effectiveness of such protocols and intervention plans of choice. This tiered meta-analysis of 66-population based studies, and 162-studywise groups, a clear pattern of ES being established across and within treatments. First, hypocaloric balance is necessary for changing body composition, but the effectiveness for establishing imbalance does not equate with the effectiveness for body compositional changes, or any biomarkers associated with metabolic issues. With analysis showing that there is a necessity to include exercise in combination with diet effectively elicit changes in body composition and biomarkers of metabolic issues. More importantly, the combination, resistance training (RT) was more effective than endurance training (ET) or combination of RT and ET, particularly when progressive training volume of 2-to-3 sets for 6-to-10 reps at an intensity of =75% 1RM, utilizing whole body and freeweight exercises, at altering body compositional measures (ES of 0.47, 0.30, and 0.40 for loss of BM, FM, and retention of FFM respectively) and reducing total cholesterol (ES = 0.85), triglycerides (ES = 0.86) and low-density lipoproteins (ES = 0.60). Additionally RT was more effective at reducing fasting insulin levels (ES = 3.5) than ET or ET and RT. Even though generally lower ES than RT, the inclusion of ET was more effective when performed at high intensity (e.g. =70% VO2max or HRmax for 30-minutes 3-4x's/wk), or in an interval training style than when utilizing the relatively common prescribed method of low-tomoderate (e.g., 50-70% VO2max or HRmax for at least equal time) steady state method, ES of 0.35, 0.39, and 0.13 for BM, FM, and FFM respectively. Thus indicating that focus of treatment should be on producing a large metabolic stress (as induced by RT or high levels of ET) rather than an energetic imbalance for adults who are overfat. © 2015 Clark; licensee BioMed Central. Source

Alvergne A.,Manchester College | Lummaa V.,University of Sheffield
Proceedings. Biological sciences / The Royal Society

The negative wealth-fertility relationship brought about by market integration remains a puzzle to classic evolutionary models. Evolutionary ecologists have argued that this phenomenon results from both stronger trade-offs between reproductive and socioeconomic success in the highest social classes and the comparison of groups rather than individuals. Indeed, studies in contemporary low fertility settings have typically used aggregated samples that may mask positive wealth-fertility relationships. Furthermore, while much evidence attests to trade-offs between reproductive and socioeconomic success, few studies have explicitly tested the idea that such constraints are intensified by market integration. Using data from Mongolia, a post-socialist nation that underwent mass privatization, we examine wealth-fertility relationships over time and across a rural-urban gradient. Among post-reproductive women, reproductive fitness is the lowest in urban areas, but increases with wealth in all regions. After liberalization, a demographic-economic paradox emerges in urban areas: while educational attainment negatively impacts female fertility in all regions, education uniquely provides socioeconomic benefits in urban contexts. As market integration progresses, socio-economic returns to education increase and women who limit their reproduction to pursue education get wealthier. The results support the view that selection favoured mechanisms that respond to opportunities for status enhancement rather than fertility maximization. © 2014 The Author(s) Published by the Royal Society. All rights reserved. Source

Karagiannis T.,Aristotle University of Thessaloniki | Boura P.,Aristotle University of Thessaloniki | Tsapas A.,Manchester College
Therapeutic Advances in Drug Safety

Dipeptidyl peptidase 4 (DPP-4) inhibitors are a relatively new class of oral antihyperglycemic agent that enhance insulin secretion by reducing degradation of endogenous glucagon-like peptide 1. Currently, sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved by the US Food and Drug Administration or the European Medicines Agency for use in patients with type 2 diabetes. Their glycemic efficacy has been well documented; however, data regarding their long-term safety are as yet inconclusive. While preclinical studies have indicated a potential cardioprotective effect of DPP-4 inhibitors, current clinical data from cardiovascular safety trials suggest a neutral effect on cardiovascular outcomes. Moreover, postmarketing experience has given rise to concerns about specific adverse events, including pancreatitis and hypersensitivity reactions. This review summarizes available evidence regarding safety of DPP-4 inhibitors. Overall, DPP-4 inhibitors appear to be a safe option for patients with type 2 diabetes. However, close pharmacovigilance is necessary to address the uncertainty regarding pancreas-related adverse events, while their potential impact on cardiovascular outcomes will be further elucidated after completion of more long-term studies. © The Author(s), 2014. Source

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