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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.

There is ample empiric evidence to indicate that oxidative stress contributes to the pathogenesis of coronary artery disease and has a key role in the onset and progression of diabetes and its complications. Diabetes leads to depletion of the cellular antioxidant defense system and is associated with an increase in the production of free radicals. Oxidative stress can be the result of multiple pathways. Some of these are related to substrate-driven overproduction of mitochondrial reactive oxygen species, advanced glycation end product formation, glucose autoxidation, and depletion of micronutrients and cellular elements with antioxidative properties. There are numerous observational studies in the literature showing a beneficial outcome of the consumption of antioxidant vitamins. However, the interventional trials portray a different picture. The divide between the robust experimental evidence of the pathogenetic role of increased oxidative load in diabetes and the overwhelming failure of antioxidants to show any health benefits in clinical trials may well be characterized as the "antioxidant paradox."