Takeaways

• Advancement in oral diabetes pharmaceuticals – achieved within the past 30 years – has given providers and patients 11 classes of medications to use in achieving glycemic control.
• Metformin remains the first line treatment, if appropriate, then, if goals are not met, oral medications are recommended for combination therapy.
• SGLT2 inhibitors should be considered in the setting of cardiovascular disease (established or at risk for), kidney disease, or heart failure as they show significant cardiovascular benefits.
• GLP-1 receptor agonists show the greatest reduction of Hgb A1C when added to Metformin therapy, even preferable to insulin.

 

Type 2 Diabetes Mellitus, a metabolic condition characterized by hyperglycemia, is commonly due to a progressive loss of insulin secretion from the beta cells of the pancreas accompanied with simultaneous insulin resistance that results in relative insulin deficiency (Inzucchi & Lupsa, 2020). Before 1923, when insulin became commercialized in the United States after groundbreaking discoveries by Dr. Frederick Banting, there was no effective treatment for diabetes, and fatal outcomes were inevitable (White, 2014). While insulin revolutionized the treatment of diabetes mellitus, the next 70 years proved barren in the way of discovery for oral medications. It was not until the 1990’s that most of the currently available treatments were developed (White, 2014).

Goals of diabetes treatment include Hgb A1c of ≤7.0 percent, which necessitates a fasting glucose of 80 to 130 mg/dL and a postprandial glucose (90 to 120 minutes after a meal) less than 180 mg/dL (Wexler, 2020).

The following is a brief review of T2DM oral medications and initial treatments.

 

Quick Guide to T2DM Oral Medications

SULFONYLUREA – Glipizide, Glyburide – stimulate beta cells in the pancreas to release more insulin into the blood. Take orally daily or multiple times daily (Agency for Healthcare Research and Quality [AHRQ], 2008).

THIAZOLIDINE (TZDs) – Pioglitozone/Actos – improves the way insulin works in the body which allows more glucose to enter into muscle and fat. Also reduce the amount of glucose production from the liver. Oral medication taken daily (AHRQ, 2008).

ALPHA- GLUCOSIDASE INHIBITORS (AGIs) – Acarbose/Precose – delays the breakdown of carbohydrates and reduces glucose absorption in the small intestine. Also, blocks certain enzymes in order to slow down digestion of some starches. Taken orally before each meal (AHRQ, 2008).

MEGLITINIDES – Repaglinide (Prandin) – works on beta cells of the pancreas to release more insulin into the blood. Taken orally before each meal, 3x/day (AHRQ, 2008).

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS(GLP-1) -Exenatide/Lixsenatide – increases insulin secretion, slows gastric emptying, and reduces postprandial glucagon. Available as short acting and long acting subcutaneous injectables only (Dungan & DeSantis, 2020).

DDP-4 INHIBITORS – Sitagliptin (Januvia) – help pancreas release more insulin after meals and lower the amount of glucose released by the liver. Orally medication taken once daily or multiple times a day (Dungan & DeSantis, 2020).

SODIUM GLUCOSE CO-TRANSPORTER 2 INHIBITORS (SGLT-2) – empagliflozin/Jardiance, Canagliflozin/ Invokana – works on the kidneys to remove excess glucose from the body but excreting it through the urine. Orally taken, usually once daily (DeSantis, 2020).

 

First line treatment: Metformin

Assuming the patient is without contraindications, Metformin remains the first line oral pharmacological treatment for T2DM recommended by the ADA, multiple international expert panels, the European Diabetic Board recommendations, and Canada’s treatment guidelines (American Diabetes Association [ADA], 2020).  Metformin provides reliable glycemic efficacy by reducing the amount of glucose produced by the liver, with minimal risks for weight gain and hypoglycemia and with good tolerance (ADA, 2020). Recommended starting dose is 500mg daily with the evening meal, increasing as needed to achieve goals to a total dose of 2000mg per day (ADA, 2020). Titrate slowly to ensure tolerance or switch to other formulation (ie: XR) as needed to combat associated GI distress.

 

Further treatment: Latest updates in Oral T2DM Medications

If A1C goals are not met after 3 months of Metformin monotherapy combined with lifestyle modifications, combination therapy is recommended (ADA, 2020). Other medications and/or treatment methods should be added according to individual risk factors, tolerance to medications, and comorbidities (ADA, 2020).

 There is benefit to specific oral medications with certain T2DM comorbidities.  Specifically, guidelines recommend the addition of SGLT2 inhibitor or GLP-1 agonist in patients with T2DM and established or highly at risk for atherosclerotic CVD, established kidney disease, or heart failure (ADA, 2020). This combination shows significant cardiovascular benefit and reduction in adverse cardiovascular events or worsening of cardiovascular conditions (ADA, 2020).

Another notable finding, SGLT2 inhibitors have additional favorable effects on hospitalizations forheart failure and decreasing risk of renal disease (ADA, 2020). However, the greatest Hgb A1C reduction was seen with the addition of a GLP-1 receptor agonist, preferable even to the addition of insulin, when added to Metformin therapy (ADA, 2020).

Perhaps most important, when making treatment decisions: include the patient. National guidelines and organizational resources urge providers to utilize patient centered decision making throughout the process of choosing a combination therapy and monitoring.

To learn the very latest and earn CE credit, register for our June 9-11 Virtual Conference, which will have several sessions on Diabetes treatment and management.

 

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References

Agency for Healthcare Research and Quality. (2008, January). Toolkit for Implementing the Chronic Care Model in an Academic Environment. Retrieved November 8, 2020, from https://www.ahrq.gov/prevention/curriculum/chroniccaremodel/chronic2a12c.html

American Diabetes Association. (2020, January 01). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Retrieved November 08, 2020, from https://doi.org/10.2337/dc20-S009

DeSantis, A., MD. (2020, October 29). Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus. Retrieved November 09, 2020, from https://www.uptodate.com/contents/sodium-glucose-co-transporter-2-inhibitors-for-the-treatment-of-hyperglycemia-in-type-2-diabetes-mellitus?search=sglt2+inhibitors

Dungan, K., MD, & DeSantis, A., MD. (2020, February 14). Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus. Retrieved November 10, 2020, from https://www.uptodate.com/contents/dipeptidyl-peptidase-4-dpp-4-inhibitors-for-the-treatment-of-type-2-diabetes-mellitus?search=DDP-4+INHIBITORS

Dungan, K., MD, & DeSantis, A., MD. (2020, October 30). Glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus. Retrieved November 09, 2020, from https://www.uptodate.com/contents/glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus?search=GLUCAGON-LIKE+PEPTIDE-1+RECEPTOR+AGONISTS%28GLP-1%29

Inzucchi, S. E., MD, & Lupsa, B., MD. (2020, August 07). Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults. Retrieved November 07, 2020, from https://www.uptodate.com/contents/clinical-presentation-diagnosis-and-initial-evaluation-of-diabetes-mellitus-in-adults?search=type+2+diabetes+mellitus+diagonsis

Wexler, D. J., MD, MSc. (2020, June 25). Overview of general medical care in nonpregnant adults with diabetes mellitus. Retrieved November 10, 2020, from https://www.uptodate.com/contents/overview-of-general-medical-care-in-nonpregnant-adults-with-diabetes-mellitus?search=Diabetes+mellitus++goals

White J. R., Jr (2014). A Brief History of the Development of Diabetes Medications. Diabetes Spectrum: a publication of the American Diabetes Association, 27(2), 82–86. https://doi.org/10.2337/diaspect.27.2.82