Metformin for diabetes prevention : update of the evidence base

Manuscript writing fees and publication fees for this manuscripts are being paid by Merck Healthcare KGaA, Darmstadt, Germany.We have conducted a narrative review based on a structured search strategy, focusing on the effects of metformin on the progression of non-diabetic hyperglycemia to clinical type 2 diabetes mellitus. The principal trials that demonstrated a significantly lower incidence of diabetes in at-risk populations randomized to metformin (mostly with impaired glucose tolerance [IGT]) were published mainly from 1999 to 2012. Metformin reduced the 3-year risk of diabetes by −31% in the randomized phase of the Diabetes Prevention Program (DPP), vs. −58% for intensive lifestyle intervention (ILI). Metformin was most effective in younger, heavier subjects. Diminishing but still significant reductions in diabetes risk for subjects originally randomized to these groups were present in the trial’s epidemiological follow-up, the DPP Outcomes Study (DPPOS) at 10 years (−18 and −34%, respectively), 15 years (−18 and −27%), and 22 years (−18 and −25%). Long-term weight loss was also seen in both groups, with better maintenance under metformin. Subgroup analyses from the DPP/DPPOS have shed important light on the actions of metformin, including a greater effect in women with prior gestational diabetes, and a reduction in coronary artery calcium in men that might suggest a cardioprotective effect. Improvements in long-term clinical outcomes with metformin in people with non-diabetic hyperglycemia (“prediabetes”) have yet to be demonstrated, but cardiovascular and microvascular benefits were seen for those in the DPPOS who did not vs. did develop diabetes. Multiple health economic analyses suggest that either metformin or ILI is cost-effective in a community setting. Long-term diabetes prevention with metformin is feasible and is supported in influential guidelines for selected groups of subjects. Future research will demonstrate whether intervention with metformin in people with non-diabetic hyperglycemia will improve long-term clinical outcomes.Publisher PDFPeer reviewe

Patient adherence to and tolerability of treatment with metformin extended-release formulation in patients with type 2 diabetes. GLUCOMP study

Introduction. Appropriate treatment of diabetes requires regular intake of recommended drugs. Multifactorial therapy, which necessitates the concomitant use of many medications, may decrease patient adherence. The purpose of the study was to assess type 2 diabetic patients’ adherence to and tolerability of metformin extended-release formulation in the outpatient setting. Materials and methods. This non-interventional study was conducted in a group of 4737 patients [including 2468 (52%) women] with mean age of 60.6 ± 9.4 years, diabetes duration of 5.6 ± 4.4 years, duration of treatment with metformin extended release formulation of 8.3 ± 12 months at an average dose of 1667 ± 350 mg. The study enrolled patients aged over 18 years with type 2 diabetes if they were treated with metformin extended- release formulation at a dose of 1500–2000 mg for less than 1 year prior to the study enrollment. The exclusion criteria included: pregnancy, breast-feeding and any contraindications for metformin treatment. Treatment adherence was assessed by a tablet count (percentage of prescribed tablets taken) and using the Morisky-Green scale. Treatment adherence was defined as follows: excellent patient adherence if > 90% of prescribed tablets were taken; good: 76–90%; moderate: 51–75%; poor: ≤ 50%. Treatment tolerability was also evaluated based on the medical history focused on gastrointestinal symptoms, as well as patient preference for using specific types of metformin. Other patient data, clinical data and laboratory test results were recorded at the beginning of the study and after 3 months. Results. After 3 months of treatment with metformin extended release formulation 96% of study subjects demonstrated excellent or good adherence. Treatment adherence was significantly lower with 2 or 3 concomitant medications as compared to one (p < 0.001). Adverse events occurred in 715 patients (15% out of 4758 patients undergoing safety analysis). The occurrence of adverse events significantly decreased treatment adherence (p < 0.001). Approximately 90% of patients declared they had preferred the use of metformin extended-release formulation. Conclusions. Metformin extended-release formulation is a suitable, well tolerated therapeutic option which helps to obtain good patient cooperation based on good adherence.

Treatment of hypertensive patients with a fixed-dose combination of bisoprolol and amlodipine : results of a cohort study with more than 10,000 patients

INTRODUCTION: Many patients need more than one antihypertensive agent for effective blood pressure (BP) control. Prescription of a fixed-dose combination (FDC) of bisoprolol and amlodipine in one tablet has been shown to significantly improve patient adherence. This non-interventional study investigated the effects on adherence and BP control of switching from a free-dose combination of the two antihypertensive substances to a FDC in a larger patient population. METHODS: Patients aged ≥18 years with essential hypertension were switched at least 4 weeks prior to study initiation from a free-dose combination of bisoprolol and amlodipine to the FDC. Dosage adjustment was implemented only if medically indicated. Adherence was assessed on the basis of the ratio of pills used to pills dispensed (%) at each visit (pill count). BP and key laboratory values were determined at baseline, 3 and 6 months. RESULTS: 10,532 patients (average age 59 years; 48% female) were recruited between 2013 and 2014; 22% of patients had type 2 diabetes and 38% had cardiovascular disease. The mean doses of the freely combined drugs prior to switching were 5.5 mg bisoprolol and 6.1 mg amlodipine once daily. The mean daily doses prescribed in the FDC were 5.8 and 6.4 mg, respectively. Pill counts at 6 months revealed a good to excellent adherence in >95% of the patients. Comparison of BP at baseline and at 6 months showed substantial changes (mean systolic BP: 147.3 vs. 130.9 mmHg; mean diastolic BP: 87.9 vs. 79.1 mmHg). Clinically relevant improvement in systolic BP was established for 82% of patients. In patients with comorbidities, switching to FDC produced a substantial improvement in BP. A total of 89 (0.7%) adverse events (AEs) were reported, including edema, headache, dizziness, bradycardia, nausea, and skin reactions. Only three AEs were classified as serious. CONCLUSION: These data from a non-interventional study in a large patient population demonstrate the benefits of prescribing a FDC of bisoprolol–amlodipine in terms of an excellent adherence and an associated improvement in control of previously elevated BP, which may be relevant in real-life practice. FUNDING: Merck KGaA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40119-015-0045-z) contains supplementary material, which is available to authorized users

Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study

Low HDL-cholesterol (<1.02 mmol/L [40 mg/dL] in men or <1.29 mmol/L [50 mg/dL] in women) occurs in about one-third of European patients with dyslipidemia and is an independent cardiovascular risk factor. Simultaneous correction of low HDL-cholesterol and high total-cholesterol and LDL-cholesterol may provide reductions in cardiovascular morbidity and mortality beyond those possible with statins alone. Nicotinic acid (niacin in the US) is the most effective means of increasing HDL-cholesterol available and has been shown to reduce cardiovascular event rates significantly. Niaspan® (prolonged-release nicotinic acid) provides a convenient, once-daily means of administering nicotinic acid. Clinical studies with Niaspan® have demonstrated marked, long-term increases in HDL-cholesterol with additional useful benefits on triglycerides, LDL-cholesterol, and lipid sub-profiles. The NAUTILUS study demonstrated the beneficial efficacy and tolerability profiles of Niaspan® in a usual-care setting. The most common side-effect of Niaspan® is flushing, which infrequently causes treatment discontinuation and which usually subsides over continued treatment. The ARBITER 2 and ARBITER 3 studies showed 1–2 years of treatment with Niaspan® plus a statin induced regression of atherosclerosis in patients with coronary artery disease. The effect of Niaspan®-statin treatment, relative to a statin alone, on clinical cardiovascular outcomes is currently under evaluation. Niaspan® represents a practical means of correcting low HDL-cholesterol, an independent risk factor for adverse cardiovascular outcomes

Patient adherence to and tolerability of treatment with metformin extended-release formulation in patients with type 2 diabetes. GLUCOMP study

Wstęp. Prawidłowe leczenie cukrzycy wymaga regularnego zażywania zalecanych leków. Wieloczynnikowa terapia, w której konieczne jest przyjmowanie wielu preparatów, może powodować spadek stopnia stosowania się do zaleceń terapeutycznych. Celem badania była ocena przestrzegania zaleceń terapeutycznych przez pacjentów oraz tolerancji leczenia u chorych na cukrzycę typu 2, leczonych w warunkach ambulatoryjnych preparatem metforminy o przedłużonym uwalnianiu. Materiał i metody. Badanie przeprowadzono w grupie 4737 chorych [w tym 2468 (52%) kobiet] w wieku średnio 60,6 ± 9,4 roku; czas trwania cukrzycy: 5,6 ± 4,4 roku; czas trwania leczenia metforminą o przedłużonym uwalnianiu 8,3 ± 12 miesięcy w średniej dawce 1667 ± 350 mg. Do badania włączono pacjentów w wieku powyżej 18. rż. z cukrzycą typu 2, jeśli przyjmowali metforminę o przedłużonym uwalnianiu w dawce 1500–2000 mg przez mniej niż 1 rok przed włączeniem do badania. Kryteria wykluczenia z badania obejmowały: ciążę, karmienie piersią, występowanie jakichkolwiek przeciwwskazań do stosowania metforminy. Przestrzeganie zaleceń oceniano w zależności od liczby zażywanych leków oraz stosując skalę Morisky’ego-Greena. Przestrzeganie zaleceń zdefiniowano w następujący sposób: bardzo dobre przestrzeganie zaleceń przez pacjenta, jeśli &gt; 90% przepisanych tabletek zostało spożytych; dobre: 76–90%; średnie: 51–75%; złe: £ 50%. Oceniano także tolerancję leczenia na podstawie wywiadu w kierunku objawów żołądkowo-jelitowych oraz preferencji pacjentów dotyczących stosowania poszczególnych rodzajów metforminy. Inne dane pacjentów, dane kliniczne i wyniki badań laboratoryjnych rejestrowano na początku badania oraz po 3 miesiącach. Wyniki. Po 3 miesiącach leczenia metforminą o przedłużonym uwalnianiu u 96% uczestników stwierdzono bardzo dobre lub dobre przestrzeganie zaleceń terapeutycznych. Przestrzeganie zaleceń było istotnie gorsze w przypadku zażywania 2 lub 3 leków w porównaniu z 1 lekiem (p &lt; 0,001). Działania niepożądane wystąpiły u 715 pacjentów. Ich obecność istotnie pogarszała  przestrzeganie zaleceń terapeutycznych (p &lt; 0,001). Około 90% pacjentów stwierdziło, że preferuje stosowanie metforminy o przedłużonym uwalnianiu. Wnioski. Forma metforminy o przedłużonym uwalnianiu jest odpowiednią opcją terapeutyczną stosowaną w celu uzyskania pożądanej współpracy z pacjentem opartej na dobrym przestrzeganiu zaleceń terapeutycznych.Introduction. Appropriate treatment of diabetes requires regular intake of recommended drugs. Multifactorial therapy, which necessitates the concomitant use of many medications, may decrease patient adherence. The purpose of the study was to assess type 2 diabetic patients’ adherence to and tolerability of metformin extended-release formulation in the outpatient setting. Materials and methods. This non-interventional study was conducted in a group of 4737 patients [including 2468 (52%) women] with mean age of 60.6 ± 9.4 years, diabetes duration of 5.6 ± 4.4 years, duration of treatment with metformin extended release formulation of 8.3 ± 12 months at an average dose of 1667 ± 350 mg. The study enrolled patients aged over 18 years with type 2 diabetes if they were treated with metformin extended-release formulation at a dose of 1500–2000 mg for less than 1 year prior to the study enrollment. The exclusion criteria included: pregnancy, breast-feeding and any contraindications for metformin treatment. Treatment adherence was assessed by a tablet count (percentage of prescribed tablets taken) and using the Morisky-Green scale. Treatment adherence was defined as follows: excellent patient adherence if &gt; 90% of prescribed tablets were taken; good: 76–90%; moderate: 51–75%; poor: ≤ 50%. Treatment tolerability was also evaluated based on the medical history focused on gastrointestinal symptoms, as well as patient preference for using specific types of metformin. Other patient data, clinical data and laboratory test results were recorded at the beginning of the study and after 3 months. Results. After 3 months of treatment with metformin extended release formulation 96% of study subjects demonstrated excellent or good adherence. Treatment adherence was significantly lower with 2 or 3 concomitant medications as compared to one (p &lt; 0.001). Adverse events occurred in 715 patients (15% out of 4758 patients undergoing safety analysis). The occurrence of adverse events significantly decreased treatment adherence (p &lt; 0.001). Approximately 90% of patients declared they had preferred the use of metformin extended-release formulation. Conclusions. Metformin extended-release formulation is a suitable, well tolerated therapeutic option which helps to obtain good patient cooperation based on good adherence

Prediabetes management in the Middle East, Africa and Russia: Current status and call for action:

Most data on the burden of diabetes and prediabetes are from countries where local infrastructure can support reliable estimates of the burden of non-communicable diseases. Countries in the Middle ..

Dose-related effect of Niaspan (500–3000 mg/day) on lipid parameters in a 25-week, double-blind, randomized trial in 131 patients with hyperlipidemia

*p < 0.05 vs placebo. Effects of placebo have been omitted for clarity. Drawn from data presented by .<p><b>Copyright information:</b></p><p>Taken from "Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study"</p><p></p><p>Vascular Health and Risk Management 2007;3(4):467-479.</p><p>Published online Jan 2007</p><p>PMCID:PMC2291331.</p><p>© 2007 Dove Medical Press Limited. All rights reserved</p

Flushing with Niaspan in the NAUTILUS trial, a 15-week evaluation of Niaspan at doses up to 2000 mg/day in 566 patients with dyslipidemia and low HDL-cholesterol managed in the usual care setting

Reproduced with permission from . Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. , 22:417-25.<p><b>Copyright information:</b></p><p>Taken from "Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study"</p><p></p><p>Vascular Health and Risk Management 2007;3(4):467-479.</p><p>Published online Jan 2007</p><p>PMCID:PMC2291331.</p><p>© 2007 Dove Medical Press Limited. All rights reserved</p