Pharmacological Approach of Type 2 Diabetes Mellitus

·  Healthy lifestyle behaviors, diabetes self-management education and support, avoidance of therapeutic inertia, and social determinants of health should be considered in the glucose-lowering management of type 2 diabetes.

  Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)[i]’[ii]’[iii]

· The glucose-lowering treatment plan may consider approaches that support weight management goals for adults with type 2 diabetes.  

Conditional Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)[iv]’ [v] 

·  For adults with type 2 diabetes, use pharmacological strategies that provide sufficient effectiveness to achieve and maintain the intended treatment goals.  

  Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)[vi],[vii] 

· Treatment modification (intensification or de-intensification) for adults not meeting individualized treatment goals should not be delayed. 

Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)^9,[viii] 

·  Medication plan and medication-taking behavior should be reevaluated at regular intervals (e.g., every 3–6 months) and adjusted as needed to incorporate specific factors that impact choice of treatment.  

 Strong Recommendation

Moderate Quality Evidence (based on observational studies)^10,[ix] 

·  Early combination therapy (oral or injectable) can be considered in adults with type 2 diabetes at treatment initiation to shorten time to attainment of individualized treatment goals.  

Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)^9,11 

·  In adults with type 2 diabetes without cardiovascular and/or kidney disease, pharmacologic agents should address both the individualized glycemic and weight goals.  

  Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)¹¹ 

·  In adults with type 2 diabetes who have not achieved their individualized glycemic goals, selection of subsequent glucose-lowering agents should take into consideration the individualized glycemic and weight goals as well as the presence of other metabolic comorbidities and the risk of hypoglycemia.   

Strong Recommendation

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)[x] 

·  In adults with type 2 diabetes with established or high risk of atherosclerotic cardiovascular disease, HF and/ or CKD an SGLT2 inhibitor or GLP-1RA is recommended, for glycemic management, improving cardiac and renal outcome and prevention of HF hospitalizations.  

Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)[xi] 

·  In adults with type 2 diabetes who have CKD (with confirmed estimated glomerular filtration rate [eGFR] of 20–60 mL/min per 1.73 m2 and/or albuminuria), an SGLT2       inhibitor should be used for minimizing progression of CKD, reduction in cardiovascular events, and reduction in hospitalizations for HF; however,         the glycemic benefits of SGLT2 inhibitors are reduced at eGFR <45 mL/min per 1.73 m2.

Strong Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)¹³ 

·   In adults with type 2 diabetes, initiation of insulin should be considered regardless of background glucose-lowering therapy or disease stage if there is evidence of ongoing catabolism (e.g., unexpected weight loss), if symptoms of hyperglycemia are present, or when A1C or blood glucose levels are very high (i.e., A1C >10% or blood glucose ≥300 mg/dL)   

Conditional Recommendation (against)

Moderate Quality Evidence (based on observational studies)[xii] 

· In adults with type 2 diabetes, glucose-lowering agents may be continued upon initiation of insulin therapy (unless contraindicated or not tolerated) for ongoing glycemic and metabolic benefits (i.e., weight, cardio-metabolic, or kidney benefits).

Conditional Recommendation  

High Quality Evidence (based on systematic reviews, randomized controlled trials, and multiple observational studies with consistent effects)¹⁴ 

·  To minimize the risk of hypoglycemia and treatment burden when starting insulin therapy in adults with type 2 diabetes, reassess the need for and/or the dose of glucose-lowering agents with higher hypoglycemia risk (i.e., sulfonylureas and meglitinides).  

Conditional Recommendation  

moderate Quality Evidence (based and multiple observational studies with consistent effects)[xiii] 

· Monitor for signs of overbasalization during insulin therapy, such as basal dose exceeding 0.5 units/kg/day, When overbasalization is suspected, a thorough reevaluation could occur promptly to further tailor therapy to the individual’s needs.  

Conditional Recommendation  

Moderate Quality Evidence (based on observational studies)¹⁴  

·  Routinely assess all people with diabetes for financial obstacles that could impede their diabetes management. Clinicians, members of the diabetes care team, and social services professionals should work collaboratively, as appropriate and feasible, to support these individuals by implementing strategies to reduce costs, thereby improving their access to evidence-based care.  

Conditional Recommendation  

Moderate Quality Evidence (based on observational studies)[xiv] 

·  In adults with diabetes and cost-related barriers, consider use of lower-cost medications for glycemic management within the context of their risks for hypoglycemia, weight gain, cardiovascular and kidney events, and other adverse effects.

Conditional Recommendation  

Moderate Quality Evidence (based on observational studies)[xv]  

·  In adults with type 2 diabetes, metabolic dysfunction–associated steatotic liver disease (MASLD), and overweight or obesity, consider using a GLP-1 RA or a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA with potential benefits in metabolic dysfunction–associated steatohepatitis (MASH) for glycemic management and as an adjunctive to healthy interventions for weight loss.

Conditional Recommendation  

Moderate Quality Evidence (based on randomized clinical trials)[xvi]^{,[xvii], [xviii], [xix], [xx], [xxi], [xxii],[xxiii].}

· In adults with type 2 diabetes and biopsy-proven MASH or those at high risk for liver fibrosis (based on noninvasive tests), pioglitazone, a GLP-1 RA, or a dual GIP and GLP-1 RA is preferred for glycemic management due to potential beneficial effects on MASH.

·  Combination therapy with pioglitazone plus a GLP-1 RA can be considered for the treatment of hyperglycemia in adults with type 2 diabetes with biopsy-proven MASH or those at high risk of liver fibrosis (identified with noninvasive tests) due to potential beneficial effects on MASH.

Conditional Recommendation