Intensification of Oral Therapy for Type 2 Diabetes
October 15, 2015 3 minutes read
By Jeff Unger, MD, FACE
Director, Unger Primary Care Concierge Medical Group, Rancho Cucamonga, CA
Dr. Unger reports no financial relationships relevant to this field of study.
SYNOPSIS: The American Association of Clinical Endocrinologists guidelines recommend initiating dual therapy with anti-hyperglycemic agents in untreated type 2 diabetes patients having A1Cs ranging from 7.6-9%. This study assessed the reasons physicians do not adhere to the guideline recommendations.
SOURCE: Qiu Y, et al. Why physicians do not initiate dual therapy as recommended by AACE guidelines: A survey of clinicians in the United States. Diabetes Res Clin Pract 2015;108:456-465.
This study surveyed 1235 primary care physicians (PCPs) and 290 specialists who reviewed the medical charts of 5995 patients with type 2 diabetes using an online survey. Each surveyed patient had an A1c of 7.6-9% at the time of diagnosis and was treated with metformin monotherapy. Survey consultants were asked 22 reasons for not initiating dual therapy for each patient. Responses were recorded using a five-point Likert scale. Relevant reasons were compared between PCPs and specialists. The five relevant reasons for not following the American Association of Clinical Endocrinologists (AACE) guidelines for newly diagnosed patients with type 2 diabetes were as follows: 1)“Metformin monotherapy is sufficient to improve glycemic control.” 2)“Monotherapy is easier to handle than dual therapy.” 3)“I believe that monotherapy and changes in lifestyle are enough for hyperglycemia control.” 4)“I recommend monotherapy before considering dual therapy.” 5)“Patient has mild hyperglycemia.” PCPs rated these reasons for not intensifying with dual therapy as being more relevant than the specialists.
COMMENTARY
This study demonstrates the bias of PCPs in regard to their failure to understand the pathogenesis and implications of early intervention for patients with type 2 diabetes. Diabetes is a chronic progressive disease state. Gastaldelli et al suggested patients diagnosed with prediabetes have lost 80% of their beta-cell function and mass. These patients are maximally insulin resistant. Failure to intensify therapy, even at the earliest stages of the disease, is misguided.
The pathogenesis of diabetes is complex. Fortunately, we have many pharmacologic targets that can mitigate the effects of hyperglycemia. Our primary objective is beta-cell salvation and preservation. The LIBRA trial demonstrated that liraglutide can improve pancreatic beta-cell mass and function in patients with newly diagnosed type 2 diabetes. Unfortunately, the effects of beta-cell preservation appear to wane shortly after the discontinuation of liraglutide. Weng et al demonstrated that newly diagnosed type 2 diabetes patients who are placed on insulin pump therapy for 2 weeks can normalize their glucose levels within 4 days (compared to 9 days for patients taking oral antidiabetes drugs). Patients in Weng’s study were medicated for 2 weeks after normalization of blood glucose levels. After 1 year, the glucagon-stimulated endogenous insulin levels for insulin-treated patients were three times greater than those patients treated with oral antidiabetes drugs. Thus, the AACE recommends early intensification of therapies targeting beta-cell preservation. Clinicians should also direct therapies toward reversing alpha-cell hypertrophy, neuroendocrine deficiencies, increased lipolysis, hepatic glucose production, insulin resistance at the site of skeletal muscles, increased renal glucose absorption, and defective GLP-1 action. Metformin cannot act alone. As clinicians, we need to give our patients a fighting chance as soon as they are diagnosed.
REFERENCES
- Gastaldelli A, et al. Beta-cell dysfunction and glucose intolerance: Results from the San Antonio Metabolism (SAM) study. Diabetologia 2004;47:31-39. Epub 2003 Dec 10.
- Unger J. Pathogenesis of type 2 diabetes. A comprehensive analysis. In: Bacghi D, Sreejayan, eds. Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome. London: Elsevier; 2012, pp. 29-42.
- Retnakaran R, et al. Liraglutide and the preservation of pancreatic ß-cell function in early type 2 diabetes: The LIBRA trial. Diabetes Care 2014;37:3270-3278.
- Weng J, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: A multicentre randomised parallel group trial. Lancet 2008;371:1753-1760.
ABSTRACT & COMMENTARY: It may not be relevant to primary care physicians. Here's why.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content