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Type 2 diabetes is a heterogeneous disease with multiple underlying pathophysiological processes. Several new antidiabetic agents are presently available for clinical use, yet very few clinical trials have been performed on the efficacy of combination pill therapy. Combination pill use is easily justified as a second-line therapy in which the advantages of added efficacy, enhanced adherence, and only modest increase in risk are recognized. In contrast, combination pill use as first-line therapy has some drawbacks, such as increased risk of hypoglycemia, difficulty in attribution of side effects to the constituents, and less than additive efficacy of the components of the pill. In general, combinations of drugs with synergistic mechanisms of action are preferable. However, the efficacy of currently available combination pills when used as first-line therapy is less than the sum of the efficacy of its components. The current guidelines recommend initiation of dual therapy in drug-naive individuals depending on baseline HbA1c at the time of diagnosis. When the HbA1c is above 8.5%-9%, the likelihood of achieving glycemic targets with a single agent diminishes sharply. These patients may be better candidates for treatment with a combination of antihyperglycemic agents as first-line therapy.

The prevalence of diabetes mellitus increases with age and causes significant morbidity and poor quality of life in older adults. To review the current literature on the diagnosis and management of diabetes in the elderly, the relevant manuscripts were identified through a MEDLINE (2000-September 1, 2010) search of the English literature. The key phrase used was diabetes in older adults or diabetes in the elderly. The literature search was limited to core clinical journals that have accessible full texts. A total of 480 manuscripts were reviewed. Managing diabetes in older adults is a challenging task. Some features of the disease are unique to the older patient. Several new antidiabetic agents are now available for clinical use, and yet very few clinical trials have been carried out in this age group. For many older adults, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goals of diabetes care in older adults are to enhance quality of life without subjecting the residents to inappropriate interventions.

Several new pharmacological agents have recently been developed to optimise the management of type 2 (non-insulin-dependent) diabetes mellitus. The aim of this article is to briefly review the various therapeutic agents available for management of patients with type 2 diabetes mellitus and to suggest a potential approach to drug selection. There are three general therapeutic modalities relevant to diabetes care. The first modality is lifestyle adjustments aimed at improving endogenous insulin sensitivity or insulin effect. This can be achieved by increased physical activity and bodyweight reduction with diet and behavioural modification, and the use of pharmacological agents or surgery. This first modality is not discussed in depth in this article. The second modality involves increasing insulin availability by the administration of exogenous insulin, insulin analogues, sulphonylureas and the new insulin secretagogue, repaglinide. The most frequently encountered adverse effect of these agents is hypoglycaemia. Bodyweight gain can also be a concern, especially in patients who are obese. The association between hyperinsulinaemia and premature atherosclerosis is still a debatable question. The third modality consists of agents such as biguanides and thiazolidinediones which enhance insulin sensitivity, or agents that decrease insulin requirements like the alpha-glucosidase inhibitors. Type 2 diabetes mellitus is a heterogeneous disease with multiple underlying pathophysiological processes. Therapy should be individualised based on the degree of hyperglycaemia, hyperinsulinaemia or insulin deficiency. In addition, several factors have to be considered when prescribing a specific therapeutic agent. These factors include efficacy, safety, affordability and ease of administration.