Tackling Type 2 Diabetes Mellitus: 2023 ADA Pharmacologic Approaches to Glycemic Treatment Updates

Mar 30, 20235 min read

Updated: Mar 30, 2023

By Justin Ramnarain, PharmD; Claudette Donatien, PharmD; Sami Barakat, PharmD; Rebecca Khaimova, PharmD, BCACP, CDCES

Introduction

In 2019, diabetes led to 1.5 million deaths and 48% of deaths occurred before the age of 70 years.(1) Uncontrolled diabetes can lead to microvascular and macrovascular complications such as heart disease, chronic kidney disease, neuropathy, retinopathy, etc.(2) Additionally, according to the Centers for Disease Control and Prevention (CDC), being overweight and/or obese were major risk factors for diabetes and diabetes-related complications. Approximately 89.8% of persons living with diabetes are overweight or obese, and therefore are at a higher risk for cardiovascular complications.(3) Due to the complications associated with diabetes, there has been a shift in the ADA guideline to select first-line agents based on the patient’s comorbidities to minimize those additional complications. This article will focus on the updates from the 2023 American Diabetes Association (ADA) Standards of Medical Care in Diabetes, primarily on the pharmacological management of diabetes with an emphasis on weight management.(4)

The recommendations are rated based on the level of evidence:

A - Based on large well-designed clinical trials or meta-analyses
B - Based on well-conducted cohort studies or care-control studies
C - Based on poorly controlled or uncontrolled studies
E - Expert consensus with conflicting or no evidence from clinical trials

Pharmacological Approaches to Glycemic Treatment

In previous years, the American Diabetes Association (ADA) and European Association for the Study of Diabetes consensus statement for the management of type 2 diabetes mellitus (T2DM) recommended metformin as the first-line treatment alongside lifestyle modifications. Then the 2022 ADA guideline recommended choosing first-line therapies depending on the patient’s comorbidities, glycemic target, as well as side effects and cost, but indicated that these generally include metformin and comprehensive lifestyle modifications.(5) Now the 2023 ADA guideline recommends healthy lifestyle behaviors, self-management education and support, as well as reviewing social determinants of health. Additionally, it recommends choosing first-line agents that are individualized to patient goals, specifically a cardiorenal risk reduction with options, such as, glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which can be found in Table 1, which provides a summary of the pharmacological approaches to glycemic treatment. By supporting this approach, hyperglycemia can continue to be managed with additional cardiovascular, renal, and weight loss benefits, furthermore, leading to a decrease in morbidity and mortality.

The 2023 guideline also includes a new section for weight management goals. One recommendation is to change the verbiage encouraging the use of nonjudgmental language between provider and patient, moving from “obese patient” to “patient with obesity” to increase patient willingness (Grade E).(6) There is a recommendation for frequent assessments of body mass index (BMI) between visits, and the frequency is dependent on patient risk factors (Grade E).(6) The guideline recommends a weight loss of 3-7% from baseline to improve diabetes and intermediate cardiovascular (CV) risk factors. It is also proven that >10% weight loss has increased benefits, if sustained ≥ 1 year or ≥ 5% sustained change in weight in patients with T2DM. (Grade B).(6) There is a recommendation for continued use of pharmacological treatment or antidiabetic treatment in patients with T2DM, such as GLP-1 RA’s or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA agents. These agents show an intermediate to very high change in weight loss >5% after 3 months of initiation (Grade A).(6) Lastly, the guideline recommends metabolic surgery in patients with BMI ≥ 35 kg/m2 who do not achieve weight loss with nonsurgical interventions or BMI ≥ 40 kg/m2 with T2DM (Grade A).(6)

Tirzepatide is a first-in-class GIP/GLP-1 RA that has shown superiority to semaglutide, which has the highest efficacy among GLP-1 RA, in hemoglobin A1c and weight reduction. In clinical trials, patients with T2DM achieved up to 2.6% HbA1c reduction and up to 12.9 kg in weight reduction. Its approval allowed for greater emphasis on weight management in the new 2023 ADA standards updates. GLP-1 RA and GIP/GLP-1 RA are associated with weight loss, and GLP-1 RA’s are associated with improved cardiovascular outcomes.(7) Currently, there is no cardiovascular outcome data available regarding GIP/GLP-1 RA. A summary of the cardiovascular and weight loss benefits associated with GLP-1 RA’s is provided in Table 2.

Table 1: Summary of the Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes – 2023 (7)

GLP-1 RA = glucagon like peptide-1 receptor agonist; CVD = cardiovascular disease; SGLT2i = sodium glucose cotransporter-2 inhibitor; TZD = thiazolidinedione; HF = heart failure; ACEi = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; CKD = chronic kidney disease; DPP4-I = dipeptidyl peptidase-4 inhibitor

Table 2: Summary of GLP-1 RA and GIP/GLP-1 RA Agents With Weight Loss and Cardiovascular Benefits

1. World Health Organization. Diabetes. https://www.who.int/news-room/fact-sheets/detail/diabetes. September 16, 2022. Accessed February 20, 2023.

2. Centers for Disease Control and Prevention. Precent Diabetes Complications. https://www.cdc.gov/diabetes/managing/problems.html. Updated November 3, 2022. Accessed February 20, 2023.

3. Centers for Disease Control and Prevention. Risk Factors for Diabetes-Related Complications.https://www.cdc.gov/diabetes/data/statistics-report/risks-complications.html. Updated September 30, 2022. Accessed March 11, 2023.

4. American Diabetes Association. Standards of Care in Diabetes - 2023. Diabetes Care 2023;46 (Suppl. 1):S140-S157.

5. American Diabetes Association. Standards of Medical Care in Diabetes - 2022. Diabetes Care 2022;45 (Suppl. 1):S125-S143.

6. ElSayed NA, Aleppo G, Aroda VR, et al. 8. obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes—2023. Diabetes Care. 2022;46(Supplement_1):S113-S124. doi:10.2337/dc23-s008.

7. ElSayed NA, Aleppo G, Aroda VR, et al. 9. pharmacologic approaches to glycemic treatment: standards of care in diabetes—2023. Diabetes Care. 2022;46(Supplement_1):S125-S143. doi:10.2337/dc23-s009.

8. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine. 2015;373(1):11-22. doi:10.1056/nejmoa1411892.

9. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine. 2021;384(11):989-1002. doi:10.1056/nejmoa2032183.

10. Dahl D, Onishi Y, Norwood P, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022;327(6):534-545.

11. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine. 2016;375(4):311-322. doi:10.1056/nejmoa1603827.

12. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (Rewind): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130.

13. Marso SP, Bain SC, Consoli A, et al. SEMAGLUTIDE and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine. 2016;375(19):1834-1844. doi:10.1056/nejmoa1607141.