September 27, 2020

Early Combination Therapy for Type 2 Diabetes

NEW YORK (Reuters Health) – The 2020 American Diabetes Association (ADA) clinical guideline stresses the importance of considering early combination therapy in patients with type 2 diabetes.

“While metformin and therapeutic lifestyle change remain the standard for new-onset diabetes diagnoses, initial combination therapy should be considered in patients presenting with hemoglobin (Hb)A1c levels >1.5 to 2 percentage points above the target, as most singular medications rarely decrease HbA1c concentrations by more than 1 percentage point,” Kacie Doyle-Delgado of St. Mark’s Hospital and St. Mark’s Diabetes Center, in Salt Lake City, told Reuters Health by email.

In a paper in the Annals of Internal Medicine, Dr. Doyle-Delgado and colleagues on the ADA’s Professional Practice Committee summarize the new ADA recommendations related to pharmacologic management of type-2 diabetes and highlight important evidence from recent large trials with cardiovascular and renal outcomes.

According to the guideline, metformin remains the preferred initial pharmacologic agent for the treatment of type 2 diabetes, but early combination therapy should be considered in some patients at treatment initiation as a strategy for extending the time to treatment failure.

Early introduction of insulin should be considered for patients who have weight loss, symptoms of hyperglycemia, or very high HbA1c (>10%) or blood glucose (16.7 mmol/L, 300 mg/dL, or higher). But glucagon-like peptide-1 receptor agonists (GLP-1 RA) are preferred over insulin when possible.

For patients who have established atherosclerotic cardiovascular disease or indicators of high risk, established kidney disease, or heart failure, a GLP-1 RA, or a sodium-glucose cotransporter-2 (SGLT2) inhibitor with demonstrated cardiovascular disease benefit is recommended.

If a patient has heart failure or chronic kidney disease, an SGLT2 inhibitor is recommended. If an SGLT2 inhibitor cannot be used, a GLP-1 RA should be administered.

Treatment selection should be based on individual patient factors, such as cardiovascular comorbid conditions, hypoglycemia risk, impact on weight, cost, the risk for side effects, and patient preferences, the authors say. Medication regimens and medication-taking behavior should be reevaluated every three to six months and adjusted as needed to incorporate these specific factors.

ADA 2020 Changes:

What is your interpretation of the recent international guidelines recommending the use of SGLT-2is in T2DM patients having ASCVD, CV risk, HF, or DKD irrespective of baseline HbA1c?

Prohibit Use of SGLT2-i Therapy, in:

  • Moderate to Severe CKD: Glucose-lowering efficacy lost with eGFR <45mL/min/1.73 m2
  • Pregnant and breast-feeding women: Risk is not known
  • Acute severe stressful conditions (hospitalization / severe illness / surgery): Risk of euDKA
  • Insulinopenic conditions, without sufficient insulin replacement: Risk of DKA

Observe Caution in:

  • Risk of volume depletion (frail elderly, concomitant loop diuretics, predisposition to dehydration / renal impairment): Monitor volume and maintain adequate hydration
  • Complicated UTIs: temporary discontinuation is recommended
  • History of recurrent UTIs: Increased risk of UTI; observe caution and counsel accordingly
  • Improper genital hygiene: Risk of Genital Tract Infections; counsel on maintaining hygiene
  • Conditions of fasting: Starvation / Dehydration predisposes to DKA with SGLT2-i
  • Concomitant use with Insulin / Secretagogues: Risk of hypoglycemia; titrate the dose
  • Atherosclerotic CAD and HF are two important manifestations of CVD in T2DM, which account for the majority of deaths in diabetes
  • Personalized medicine approach and guidelines suggest preferential use of SGLT2-i agents, in patients with risk of atherosclerotic CVD or HF in diabetes
  • Empagliflozin has demonstrated benefits for CVD events as well as mortality outcomes, in patients with Atherosclerotic CVD and T2DM
  • Optimize clinical considerations of risk-benefit for each agent, in the principle of individualized approach for every patient

Although the guideline focuses on pharmacologic treatments, it emphasizes that the mainstay for initial treatment of type-2 diabetes includes therapeutic lifestyle change.

The clinical guideline also includes detailed algorithms for the overall approach to glucose-lowering medication and for the intensification of injectable therapies.

The full position statement is available at

SOURCE: Annals of Internal Medicine, online September 1, 2020.

Reuters Health Information © 2020

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