Exenatide plus metformin compared to metformin alone on β-cell function in patients with Type 2 diabetes
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia Metabolic Unit, Regional Hospital, Varese Ospedale Pesenti Fenaroli, Alzano Lombardo, Bergamo Hospital Centre of Diabetes, Sant'Angelo Lodigiano, Lodi RSA Villa Mafalda, Borgo San Siro, PAVIA Fondazione Ospedale della Carità, Casalbuttano, Cremona, Italy. Diabetic Medicine
(Impact Factor: 3.12).
04/2012; 29(12). DOI: 10.1111/j.1464-5491.2012.03699.x
Diabet. Med. 29, 1515–1523 (2012)
Aim To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone.
Methods A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation.
Results Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.
Conclusion Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation.
Available from: Aljoša Bavec
- "Considering that diabetes per se is a risk factor for acute pancreatitis, it is not yet established whether exenatide can induce this serious adverse event (Ahrén, 2011). Exenatide significantly improves glycaemic control and shows greater decrease in body weight if used in combination with metformin (Derosa et al., 2012). Exenatide long-acting formulation Ex(OW) results in greater improvements in glycemic control compared with regular exenatide, but shows lower HbA1c reductions compared with liraglutide once daily (DURATION program) (J.B. "
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ABSTRACT: Insulin therapy remains the standard of care for achieving and maintaining adequate glycemic control, especially in hospitalized patients with critical and noncritical illness. Insulin therapy is more effective against elevated fasting glycaemia but less in reduction of postprandial hyperglycaemia. It is associated with a high incidence of hypoglycemia and weight gain. Contrary, GLP-1 mimetic therapy improves postprandial glycaemia without the hypoglycaemia and weight gain associated with aggressive insulin therapy. Moreover, it has potential to reduce cardiovascular related morbidity. However, its increased immunogenicity and severe gastrointestinal adverse effects present a huge burden on patients. Thus, a right combination of basal insulin which has lowering effect on fasting plasma glucose and GLP-1 mimetic with its lowering effect on postprandial plasma glucose with minimal gastrointestinal adverse effects, seems the right therapy choice from a clinical point of view for some diabetic patients. In this article, we discuss the pros and cons of use of insulin analogues and GLP-1 mimetics that are associated with the treatment of type 2 diabetes.
Available from: José G B Derraik
- "The observed 28% improvement in disposition index is consistent with this observation. Comparatively, studies in diabetic adults (who are likely to have an exaggerated response to therapy) have shown that mainstream medications affecting only β-cell secretion capacity have achieved improvements of 55% (dipeptidyl peptidase-4 antagonists)  and 100% (glucagon-like peptide-1 agonists) . Hence, compared to these drugs that only improve insulin secretion, OLE improves both insulin sensitivity and pancreatic β-cell secretory capacity. "
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ABSTRACT: Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans.
To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men.
Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4±5.5 years and BMI 28.0±2.0 kg/m(2)) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness.
Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function.
Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome.
Australian New Zealand Clinical Trials Registry #336317.
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ABSTRACT: The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double-blind, placebo-controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA(1c) ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA(1c) by -17.5%, FPG by -12.7%, PPG by -20.5%. Regarding insulin resistance, sitagliptin decreased FPI by -8.3% and HOMA-IR by -20.0%, confirming that what have been already reported in short-term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by -4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by -13.3%, LDL-C by -20.4%, and Tg by -32.3%, and also increased HDL-C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile.
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