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New Direction in Drug Treatment Selection for Type 2 Diabetes

Scientific understanding of the disease shifts treatment to drugs with newer mechanisms…. 

Over the past 15 years there have been dramatic changes in both what drugs are prescribed and how they are used in treating type 2 diabetes. A lot of this is a result of the new classes of drugs that have been developed. Other changes include the types of combination therapies and the rate at which they are utilized. Other aspects to factor in are the impact of advertising and marketing by pharmaceutical companies as well loss of patent protection for previously utilized drugs.

By understanding the dynamic pathways that govern insulin secretion and glucose regulation, new drugs with new mechanisms of action have been developed and subsequently their use has greatly increased. Of note are the DPP-4 inhibitors and GLP-1 agonists. Since their launch in 2006, DPP-4 inhibitors such as Januvia® and Onglyza® have accounted for 21% of treatment visits that involved their use. Promotion of these classes of drugs as well as their favorable adverse effect profile (such as being weight-neutral or causing weight loss) can be accredited for their increased use. Their long-term effects, however, are yet to be evaluated and recent concerns of pancreatitis and pancreatic cancer have risen.

Among older and established drugs, metformin use increased from 23% in 1997 to 53% in 2012 but has plateaued since 2010. The glitazones which include pioglitazone (Actos®) have seen their use decrease from a peak of 41% in 2005 to 16% in 2012. This can to an extent be attributed to their link to cardiac issues and bladder cancer causing a substantial decrease in physicians prescribing it. Sulfonylureas like glipizide and glyburide have seen their use fall the greatest, with 61% of treatment visits utilizing them in 1997 versus only 22% in 2012. This is attributed to their association with hypoglycemia and weight gain as well as loss of patents and promotion.

Overall, insulin use has remained constant over the past 15 years. However, the differences in treatment patterns lie within the differing durations of action of different insulins. The use of ultralong-acting insulins such as glargine (Lantus®) and detemir (Levemir®) has increased dramatically from <1% in 1997 to 18% in 2012. By the same token, the use of very short-acting insulins (aspart or Novolog®, and lispro or Humalog®) have increased modestly. Regular insulin and intermediate-acting insulin (NPH insulin) use has decreased in that same timeframe.

The use of combination therapy has increased dramatically as well, by nearly 40% in the past 15 years. The majority of dual therapies used included metformin and a sulfonylurea or a glitazone and this can be chalked up to the amount of clinical evidence available for their use in combination. However, other less-studied combinations have been used such as DPP-4 inhibitors with sulfonylureas, and their use as such can be considered risky due to increased incidences of hypoglycemia.

Practice Pearls:

  • Metformin remains the cornerstone of type 2 diabetes therapy, with over 50% of physician visits involving its use.
  • Sulfonylurea and glitazone use have decreased and primarily been replaced by the DPP-4 inhibitors which now account for over one-fifth of treatment visits.
  • Ultralong-acting insulin use has increased dramatically and very short-acting insulin use has increased modestly.
  • Combination therapy remains a cornerstone due to clinical guideline support. This includes the use of combinations like DPP-4 inhibitors with sulfonylureas but these can sometimes raise concerns such as increased hypoglycemia.
Diabetes Care, November 2013