Figure 4 presents the principal mechanisms, advantages and disadvantages, and the relative costs of four of the classes of medications that we have for T2DM treatment in clinical practice.[2]

The first agent listed is metformin, ie, the most commonly used of the biguanides, which have a mechanism of action that leads to a decrease in hepatic glucose production. The advantages of metformin are particularly the extensive clinical experience we have with it, it does not produce hypoglycemia, and it maintains weight neutrality. There are also positive data suggesting that it may lower cardiovascular events, but these data remain questionable.

The disadvantages include gastrointestinal side effects, which can be severe for some people, to the point where they cannot use this class of medications because of intractable diarrhea. We also know that with long-term use and high doses (≥2 g/day) of metformin, a vitamin B₁₂ deficiency will develop as a result of malabsorption, and lactic acidosis has also been documented in some patients.

So there are some clear-cut contraindications for the use of metformin, but other advantages of this agent are its ready availability and low cost.

The second class of agents in Figure 4 is the sulfonylureas/meglitinides, which increase insulin secretion at the level of the β-cells. As with the biguanides (metformin), there is extensive clinical experience with this class of medications, they are readily available, and the cost is quite low. There may be some microvascular and cardiovascular risks associated with this class of drugs, and in the case of the meglitinides the risk may be moderate-to-high. Finally the one clear-cut disadvantage with this class of medications is weight gain, so we should be cautious about ordering sulfonylureas for patients who may already be overweight.

The thiazolidinediones (TZDs) work by increasing insulin sensitivity, and this class of drugs represents the best insulin sensitizers that we have. The advantages of this class include its lack of association with hypoglycemia, some favorable lipid effects (lowering triglycerides and increasing HDL-cholesterol), and durability of glycemic control, apparently greater than for either metformin or the sulfonylureas.

Clear-cut disadvantages of the TZDs include weight gain and edema. TZDs can cause edema, both pulmonary as well some peripheral, and this class of drugs cannot be used in patients with NYHA class III or IV heart failure. Pioglitazone in particular may have a causative relation with bladder cancer, and a possible increased risk of myocardial infarction (MI) with rosiglitazone was well documented several years ago. Finally a risk of long-bone fractures may be associated with this class of drugs.

Finally, although the TZDs have been available for a while and we have a lot of experience with them, the cost of these drugs is still pretty high.

The α-glucosidase inhibitors represent a class of non-systemic medications that slow the rate of digestion of dietary carbohydrate in the gut. The clear advantages with this class of drugs are that they do not produce hypoglycemia and they help lower the postprandial glucose readings. Although demonstrated conclusively, it has been suggested that this drug class may also lowering the risk of cardiovascular events.

A clear-cut disadvantage with the α-glucosidase inhibitors. and one of the reasons why it is hard to maintain adherence in patients taking these drugs, is the gastrointestinal side effects. It is also associated with no more than a modest lowering of HbA_1C. On the other hand, these drugs are associated with moderate cost. Kapustin J. J Nurse Pract. 2014; 00:00 – 00.