Type 2 diabetes mellitus

Management

• See also Diabetes mellitus

Medical Management

• At diagnosis: lifestyle changes, with nutritional therapy, weight management, and physical activity, and consider adding metformin
• Determine A1c target (≤7% for most people)
  • A1c <1.5% above target
    • Reassess after 3 months of lifestyle changes
    • If not at target, add metformin
  • A1c ≥1.5% above target: start metformin immediately, and consider concurrent second agent
  • Symptomatic hyperglycemia or metabolic decompensation: start metformin and insulin
• If not at target and has clinical CVD: add empagliflozin, liraglutide, or canagliflozin
• If still not at target, add additional agents based on individualized considerations
  • Avoidance of hypoglycemia and/or weight gain with adequate glycemic efficacy: DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors
  • Reduced eGFR or albuminuria
  • Clinical CVD or CV risk factors
  • Degree of hyperglycemia
  • Other comorbidities, such as heart failure, cardiovascular disease, kidney disease, or liver disease
  • Planning pregnancy
  • Cost to patient
  • Patient preference

Class	CVD Outcomes	Hypoglycemia	Weight	A1c Lowering	Other Considerations	Cost
GLP-1 receptor agonists	liraglutide is superior in T2DM, LAR and lixiglutide are neutral	rare	↓↓	↓↓ to ↓↓↓	GI side effects, gallstones; contraindicated in personal/family history of medullary thyroid cancer or MEN-2; given by subcutaneous injection	$$$$
SGLT2 inhibitors	canagliflozin and empagliflozin are superior in T2DM	rare	↓↓	↓↓ to ↓↓↓	urogenital infections, hypotension, dose-related changes in LDL; caution with renal dysfunction, loop diuretics, and the elderly; dapagliflozin contrindicated in bladder caner; rarely caused euglycemic diabetic ketoacidosis; increased risk of fractures or amputations with canagliflozin; reduced progression of nephropathy and heart failure exacerbations with canaglizflozin and empagliflozin	$$$
DPP-4 inhibitors	↔	rare	↔	↓↓	avoid saxagliptin in heart failure; rare joint pain	$$$
insulin	↔	yes	↑↑	↓↓ to ↓↓↓↓	no dose ceiling; requires subcutaneous injection	$ to $$$$
thiazolidinones	↔	rare	↑↑	↓↓	CHF, edema, fractures, rare bladder cancer with pioglitazone, cardiovascular controversy with rosiglitazone, 6-12 weeks for maximum effect	$$
alpha-glucosidase inhibitors		rare	↔	↓	GI side effects common; TID dosing	$$
meglitinide		yes	↑	↓↓	lower glucose rapidly; reduced postprandial glycemia; TID to QID dosing	$$
sulfonylureas		yes	↑	↓↓	gliclazide and glimepiride have less hypoglycemia than glyburide; poor durability	$
orlistat		none	↓	↓	GI side effects; TID dosing	$$$

Target A1c

• ≤6.5% for adults with T2DM to reduce with risk of CKD and retinopathy, if at low risk of hypoglycemia
• ≤7% for most adults with T1DM and T2DM
• 7.1-8% for functionally dependent elderly
• 7.1-8.5% for those with recurrent severe hypoglycemia or hypoglycemia unawareness
• 7.1-8.5% for those with a limited life expectancy (stop measuring, and target euglycemia for symptom control)
• 7.1-8.5% for those the frail elderly or those with dementia