Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population

Aims/hypothesis Insulin resistance is associated with abnormalities in lipid and glucose metabolism, which are major components of metabolic syndrome and risk factors for vascular disease. This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor α/γ agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance. Methods A 12 week, multicentre, randomised, double-blind, placebo-controlled, dose-finding study compared the efficacy and safety of oral tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7 mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for women). Results A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: −43% to −30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: −20% to −10%; p<0.0001) and NEFA by 40% (95% CI: −51% to −27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to −24%; p<0.0001). At the end of treatment there was a dose-dependent increase in patients with pattern A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0 mg). Tesaglitazar produced significant reductions in fasting insulin concentration (−35%; p<0.0001) and plasma glucose concentration (−0.47 mmol/l; p<0.0001). Respiratory infection and gastrointestinal symptoms were the most common adverse events and were similarly frequent in all groups. Conclusions/interpretation Tesaglitazar was well tolerated and produced significant, dose-dependent improvements in lipid and glucose metabolism and insulin sensitivity. Tesaglitazar may have the potential to prevent vascular complications and delay progression to diabetes in these patients