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RESEARCH: Dean T Eurich, Finlay A McAlister, David F Blackburn, Sumit R Majumdar, Ross T Tsuyuki, Janice Varney, and Jeffrey A Johnson Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review BMJ 2007; 335: 497 [Abstract] [Full text]

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Insulin treatment seems not rational

Philipp Conradi   (20 October 2007)

Renal Failure in Heart Failure

Mahmood Ahmad, Rizwan Mahmood   (31 October 2007)

Metformin is safe also in older diabetic patients with heart failure

Andrea Corsonello, Filippo L. Fimognari, Raffaele Antonelli Incalzi   (1 February 2008)

Insulin treatment seems not rational 20 October 2007
Philipp Conradi, GP Otto-Dix-Ring 98 01219 Dresden, Germany Send response to journal: Re: Insulin treatment seems not rational	The authors are to be applauded for putting further evidence on the marginal benefits of insulin treatment in type II diabetic patients. This evidence however does not come as a surprise since Greenhalgh correctly interpreted the UKPDS results in the late 90s and pointed to the absence of macrovascular benefits coupled with poor general performance and average weight gain of 3,5 Kg despite good blood sugar control in patients treated with insulin. The triad of hyperinsulinism, adiposity and insulin resistance is commonly referred as the metabolic syndrome related to increased cardiovascular morbidity. This concern however is not applied to overweight diabetic patients with increasing insulin doses by worsening resistance. Insulin treatment therefore seems not quite rational for a variety of diabetic patients. Up to now however there is only limited acceptance for deconverting insulin treatment despite emerging evidence with, for example, Pioglitazone as a possible candidate ( Pfützner in Mainz/ Germany - Poster at the ADA 2006). Future research in diabetology and in primary care might focus on finding the correct patients who benefit from being taken off insulin. Competing interests: I have no interests to declare
Renal Failure in Heart Failure 31 October 2007
Mahmood Ahmad, ST3-LAT Medway Maritime Hospital, Gillingham, Kent , ME7 5NY, Rizwan Mahmood Send response to journal: Re: Renal Failure in Heart Failure	An interesting contradiction is the fact that many patients in heart failure can develop worsening renal failure due to the Heart failure itself and also due to the drugs they are given e.g Furosemide, Metalzone etc. This can be during their Hospital stay when they are on large doses to reduce the amount of fluid in their body. A study in Diabetic Medicine in 1999 in 308 Type 2 DM patients admitted to Hospital showed Renal impairment was present in 19 % of patients who had been prescribed with Metformin (1) Holstein A, Nahrwold D, Hinze S, Egberts EH. Diabet Med. 1999 Aug;16(8):692-6 Competing interests: None declared
Metformin is safe also in older diabetic patients with heart failure 1 February 2008
Andrea Corsonello, Junior consultant Istituto Nazionale di Ricovero e Cura per Anziani (INRCA), I-87100 Cosenza, Italy, Filippo L. Fimognari, Raffaele Antonelli Incalzi Send response to journal: Re: Metformin is safe also in older diabetic patients with heart failure	Eurich et al recently reported improved survival in metformin-treated diabetics with HF(1). Evidence also showed that metformin has a favourable profile of efficacy and safety when compared with other oral antidiabetic drugs. Of special interest is the finding that, contrary to the common belief, metformin does not carry an excess risk of lactic acidosis in patients with heart failure (HF)(2). This evidence makes questionable the currently reported contraindication to the use of metformin in HF (3). We retrospectively analysed the relationship between metformin use and survival in a population over 65 years with diabetes mellitus and HF in II (n=104), III (n=90) or IV (n=10) New York Hearth Association class, and with a high prevalence of comorbid conditions contraindicating metformin use or increasing the risk of adverse reactions according to the producer (3) (renal failure: 22.6%, peripheral vascular disease: 7.7%, liver disease: 24.0%, chronic obstructive pulmonary disease: 22.6%). Patients (mean age 78.5+/-6.9 years, range 65-97 years, 45.2% males) had been enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano Study (4). They were very frail as testified by limitations in personal capabilities (dependency in at least 1 Activities of Daily Living: 25.0%; dependency in at least 1 Instrumental Activities of Daily Living: 92.8%) and cognitive performance (Abbreviated Mental Test score<7: 22.1%), and were followed-up for 1 year after hospitalization for HF. In this period, 32 patients (15.4%) regularly took metformin, and 41 died. Among persons who died, 5 were using metformin (15.6% of metformin users) and 36 were not (20.4% of non-users). After adjusting for potential confounders (age, gender, comorbidity, New York Hearth association class, use of renin- angiotensin system inhibitors, beta-blockers, K+-sparing diuretics and insulin, and diagnosis of renal failure based on serum creatinine) metformin use was associated with a not significant increase in survival (Hazard Ratio 0.85, 95% CI 0.32-2.23). The incidence of adverse drug reactions did not distinguish metformin from non metformin users (3.1% vs. 2.8%, p=0.969). Hypoglycaemia occurred only in 2 patients among non users of metformin. No case of lactic acidosis was recorded. Metformin produces cardiovascular benefits by improving myocardial glucose utilization, and by reducing endothelial dysfunction, inflammation and oxidative stress (5). Our "real world observation" adds to the notion that metformin may not be deleterious in diabetic patients with HF and suggests that it can be safely prescribed even to elderly and frail HF patients. Acknowledgments The GIFA study is partially supported by a grant 94000402 from the Italian National Research Council, Rome, Italy. References 1. Eurich DT, McAlister FA, Blackburn DF, Majumdar SR, Tsuyuki RT, Varney J, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review. BMJ 2007; 335(7618): 497. 2. Bolen S, Feldman L, Vassy J, Wilson L, Hsin-Chieh Y, Marinopoulos S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007; 147: 386- 99. 3. American Society of Health-System Pharmacists: AHFS Drug Information. Bethesda, MD, American Society of Health-System Pharmacists, 2004 4. Carosella L, Pahor M, Pedone C, Zuccalà G, Manto A, Carbonin P. Pharmacosurveillance in hospitalized patients in Italy. Study design of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA). Pharmacol Res 1999: 40:287-295 5. Masoudi FA, Inzucchi SE. Diabetes mellitus and heart failure: epidemiology, mechanisms, and pharmacotherapy. Am J Cardiol 2007; 99:113B- 132B Competing interests: None declared