Metformin in the diabetic elderly patient: an old, safe and effective treatment

Over-65 diabetics represent about half of the patients visiting general practitioners. Although diabetes pathogenesis in geriatric and young age are similar, treatment gold standards and clinical conditions are extremely variable, requiring a more individualised approach.¹ In this context, a recent review points out that there is no clear evidence for the optimal glycaemic target in the elderly patient and that patient’s preferences and pharmacologic burden must be taken into consideration, within the therapeutic choices, together with the possible risks and benefits associated to single treatments.² This study also suggests a HbA1c value between 7.5% and 9.0% as optimal glycaemic target in the elderly patient.

Adapted by bibliographic reference 2

Particularly in the elderly patient, the onset of hypoglycaemia is often associated with severe consequences and is facilitated by several factors, such as polypharmacy and the risk of subsequent interactions, the mistakes caused by the reduced ability of handling medicines, the inability of evaluating the relation between ingested carbohydrates and the therapy, the scarce symptomatology of neuropathies and the reduced adrenergic reaction.³ Hypoglycaemia absolute risk increases with age, therefore in elderly diabetics it is often preferable to avoid intensive hypoglycaemic treatments that increase the risk of hypoglycaemia⁴ whilst low hypoglycaemia risk treatments should be privileged, even at the expense of a less than optimal glycaemic control. In this context, metformin, a medicine available on the market since 1950, is nowadays considered the first choice treatment in the elderly patient, despite the numerous other therapeutic options available.
Unlike other secretagogue drugs, metformin does not act directly on the beta cells nor, therefore, on the rapid insulin release, but on the counter-regulatory processes reactivating tissue insulin sensitivity. For this reason, the hypoglycaemic risk associated to this drug is very low. Metformin showed to be effective in reducing both micro and macrovascular complications induced by diabetes, influencing the myocardial heart failure rate and the global and diabetes-related mortality.⁵ The direct cardiovascular protection is mediated by the reduction of the levels of triglycerides, cholesterol LDL, body weight and plasmatic levels for some inflammatory molecules involved in several processes linked to cellular ageing and carcinogenesis.⁶ Metformin can also determine a reduction of the body weight and this is particularly important in the elderly, often affected by metabolic syndrome, central obesity, hypomobility and under incorrect alimentary regime. Besides, the minimal bonding with plasma proteins and the absence of active metabolites decreases the risk of pharmacological interactions. It is important to note, to conclude, that since metformin is not an insulin-releasing drug, it is not necessary to administer it before meals, that the 80% of its maximum effectiveness is delivered with a daily dose of 1,500 mg and that it can be easily associated to other antidiabetic drugs.
The use of metformin in the elderly patient is limited by some contraindications such as renal failure, because of the increased risk of lactic acidosis associated to this condition. It should be however reminded that it is not an absolute contraindication and that metformin-induced lactic acidosis is actually a very rare complication, estimated as 1 over 23,000-30,000 person-years in respect to 1 over 18,000-21,000 person-years who use antidiabetics other than metformin. Literature data indicate however that the passage from metformin to other hypoglycaemic drugs increases the risk of hypoglycaemia or heart failure in patients with renal failure⁷ Meta-analysis show that even though its clearance is reduced in presence of renal failure, metformin remains in the therapeutic range up to clearance values higher than 30 ml/min without influencing the lactate plasma levels. Using the drug more carefully in complex patients and when factors potentially increasing the risk of lactic acidosis are present, metformin can therefore represent a valid therapeutic option up to the last stages of renal failure (see table).

Adapted from reference 8

Nausea, vomit and diarrhoea remain the side effects most commonly associated with the drug, even though they are generally moderate and temporary. Postprandial administration, possible dose reduction and extended release formulation determine a neat improvement in the drug tolerability.⁹ Its anorectic effect should also be noted, which is part of its therapeutic action and limits its use in malnourished or underweight elderly patients.
In conclusion, considering the present evidences and the different therapeutic goals for the elderly patient, with some precautions metformin remains an extremely manageable and economic drug - despite having been on the market for 50 years and despite new hypoglycaemic drugs being available - a drug with an optimal pharma kinetics profile and also useful in terms of cardiovascular prevention. To date, no therapy in the diabetic elderly patient can be considered safe a priori; the five principal variables that affect the therapeutic choice are: cognitive and motor integrity, cardiovascular risk profile, co-existent diseases, diabetes-induced complications and level of dependence from the caregiver. Metformin, used rationally, satisfies the general goals of diabetes therapy in the elderly patient, remaining a manageable and economic drug, with a good risk-benefit profile.