Figure 2: Pharmacologic Approaches to Managing Adults with Type 2 Diabetes: Glycemic Control and Weight Loss Diabetes Self-Management Education and Support (DSMES): Goal: Achievement and Maintenance of Glycemic Control and Weight Reduction Glycemic Management Achievement of Weight Management
• Metformin or agents including combination therapy that provides adequate efficacy to achieve and maintain treatment goals. • Make avoidance of hypoglycemia a priority.
• Medical nutrition therapy (MNT). • Physical activity.
• For weight loss, consider medication or metabolic surgery. • When considering glucose-lowering therapies, use regimens with high to very-high dual glucose and weight efficacy.
Efficacy Approaches for Glucose Lowering
Efficacy Approaches for Weight Loss
Very High: • Dulagutide (high dose). • Semaglutide, Tirzepatide. • Combination or noninsulin agents and injectable insulin. High: • GLP-1 RA; Metformin; SGLT-2i, Sulfonylurea; thiazolidinedione. Intermediate: DPP-4.
Very High : • Semaglutide, Tirzepatide. High : • Dulaglutide, Liraglutide. Intermediate : • GLP-1 RA, SGLT-2i. Neutral : • DDP-4; Metformi n.
Note. From ElSayed et al., 2023a.
Mechanism of action Metformin improves glycemic targets through several mechanisms. Metformin primarily works in the liver by inhibiting hepatic gluconeogenesis, reducing glucose absorption from the intestines, and improving insulin sensitivity in muscle and fat cells (Baker et al., 2021). Metformin reduces fasting blood glucose (FBG) and insulin levels by inhibiting hepatic gluconeogenesis. With a reduction in insulin levels, metformin helps improve insulin sensitivity. Other actions, such as decreased intestinal absorption of glucose and decreased fatty acid oxidation,
also contribute to metformin’s antihyperglycemic effect. Most of metformin’s glucose-lowering action occurs in the gastrointestinal (GI) tract rather than in circulation. Research has also found that metformin alters the gut microbiome, increasing GLP-1 secretion and improving glucose homeostasis. Unlike some antihyperglycemic agents like sulfonylureas, metformin rarely causes hypoglycemia and is weight neutral (Baker et al., 2021).
Evidence-Based Practice Metformin is considered one of the initial pharmacological therapies for patients with type 2 diabetes. Glycemic efficacy, absence of weight gain, no hypoglycemia, general tolerability, long-term safety, and low cost are benefits of using metformin. Metformin can be initiated at diagnosis, along with lifestyle interventions. For highly motivated patients with A1Cs near the target range (7%), a three- to six-month trial of lifestyle modifications before initiating metformin is reasonable. For patients with recurring hyperglycemia and A1Cs >7.5%, several other noninsulin antihyperglycemic agents or noninsulin injectables are available to be used with metformin (White, 2022).
Side effects Metformin is tolerated well but can cause gastrointestinal upset like bloating, abdominal discomfort, nausea, vomiting, and diarrhea anytime during therapy. These side effects are typically dose related, and the dose is adjusted downward to one that doesn’t cause side effects. In some cases, gastrointestinal upset may take months to occur. For this reason, metformin is taken with a meal, usually started at a low dose (500 mg daily) and increased gradually every week to the desired dose. Metformin may be used safely in patients with a reduced estimated glomerular filtration rate (eGFR >30 mL/min/1.73 m 2 ). However, metformin is contraindicated in patients with advanced renal impairment or congestive heart failure (Odegard & Capoccia, 2022).
Although rare, lactic acidosis is a risk for patients on biguanides. Conditions that might predispose patients to lactic acidosis include liver disease, impaired kidney function, congestive heart failure, sepsis, and any diagnostic test that uses iodine contrast media. Thus, it is wise to discontinue metformin before diagnostic tests and surgery and resume it after normal kidney function can be determined with laboratory analysis. Patients taking metformin may also experience intestinal malabsorption of vitamin B12. Low vitamin B12 could potentially lead to an increased prevalence of peripheral neuropathy. As a precaution, regular testing of vitamin B12 levels in patients taking metformin is suggested. In addition, an oral supplement may be recommended in patients with low vitamin B12 (Odegard & Capoccia, 2022).
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Book Code: RPTTX2024
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