The American College of Physicians (ACP) has this month released an updated guideline on the oral management of type 2 diabetes mellitus (T2DM). This new guideline replaces the 2012 guideline and has been endorsed by the American Academy of Family Physicians.  The rapidly expanding medication options have perplexed providers and patients alike. 29 million Americans live with T2DM with the risk and prevalence increasing with age. Over 26% of Americans over the age of 65 for instance, have T2DM. The obesity epidemic in the US has had major contribution to the T2DM prevalence. The costs of managing T2DM is staggering, over $245 billion in 2012.

Unlike Type 1 diabetes mellitus where insulin is the first line therapy, people with type 2 diabetes mellitus are most commonly started and managed in an ongoing way with oral medications. These oral medications fall into five classes:

• Biguanides (metformin)
• Sulfonylureas (e.g. glipizide, glyburide, glimepiride)
• Thiazolidineodiones (TZD) (e.g. pioglitazone, rosiglitazone)
• DPP-4 inhibitors (e.g. sitagliptin, linagliptin, saxagliptin)
• Sodium-glucose co-transport-2 inhibitors (SGLT-2) (e.g. canaglifozin, empaglifozin)

The evidence review by ACP was conducted using the AHRQ evidence review methodology and compared monotherapy versus combination therapy. The take home lessons from this evidence review and guideline are:

• Most drugs reduced A1C to similar levels
• Metformin is more effective in reducing weight gain than other classes, and more effective still when combined with an SGLT-2 medication
• All medications have signification side effects including:
  • Metformin is associated with GI upset
  • SU have increased risk of hypoglycemia
  • TZD have increase risk of heart failure
  • SGLT-2 have increased risk of mycotic infections, esp. genital mycotic infections
• SGLT-2 medications lose their efficacy as renal function declines (GFR < 60)
• Metformin is safe even in patients with mild chronic kidney disease but remains contraindicated in patients with GFRs < 30 ml/min/1.73m²
• Non-pharmacologic therapy- dietary modification, wt loss, exercise- remain critically important

ACP provided two recommendations in this new guideline:

1. Metformin is first line of therapy when oral medications are needed for patients with type 2 diabetes mellitus
2. When a second agent is needed for tighter blood glucose control, a sulfonylurea, TZD, DPP-4 or SGLT-2 medication should be added. These should be selected based upon patient characteristics and clinical considerations. For example
   1. Avoid TZD in heart failure patients
   2. When avoiding weight gain is important, consider SGLT-2
   3. In patients with history of mycotic genital infections, avoid SGLT-2
   4. In patients with pre-existing joint disease, avoid DPP-4

Given the high prevalence of type 2 diabetes in Medi-Cal populations, PHC recommends:

• Initiate oral therapy with metformin

• When a second line of therapy is required, consider sulfonylureas or TZD which have more extensive safety and efficacy data before moving to DPP-4 or SGLT-2 except when above clinical considerations are present