From the Guidelines
Medication treatment for type 2 diabetes mellitus (T2DM) should begin with metformin as the first-line therapy, with a recommended initial dose of 500mg once or twice daily, gradually increasing to 1000mg twice daily as tolerated, as supported by the most recent guidelines 1.
Initial Therapy
Metformin is the preferred initial pharmacologic agent due to its efficacy, safety, and potential to reduce the risk of cardiovascular events and death 1. It works by decreasing glucose production in the liver and improving insulin sensitivity.
Combination Therapy
If metformin alone is insufficient to control blood glucose levels, additional medications may be added, including:
- Sulfonylureas (like glipizide or glimepiride)
- DPP-4 inhibitors (sitagliptin, linagliptin)
- SGLT-2 inhibitors (empagliflozin, dapagliflozin), which have been shown to reduce all-cause mortality and major adverse cardiovascular events (MACE) compared to usual care 1
- GLP-1 receptor agonists (semaglutide, dulaglutide), which have also been shown to reduce all-cause mortality and MACE compared to usual care 1
- Thiazolidinediones (pioglitazone)
Individualized Treatment
Treatment should be individualized based on factors such as:
- Cardiovascular risk
- Kidney function
- Risk of hypoglycemia
- Cost considerations
- Patient preferences Regular blood glucose monitoring is essential, with a target HbA1c of less than 7% for most patients, though goals may be adjusted based on individual circumstances.
Special Considerations
For patients with chronic kidney disease (CKD), the KDIGO 2022 clinical practice guideline recommends first-line treatment with both metformin and an SGLT2 inhibitor, with additional drug therapy as needed for glycemic control 1.
From the FDA Drug Label
INVOKANA (canagliflozin) has been studied as monotherapy, in combination with metformin HCl, sulfonylurea, metformin HCl and sulfonylurea, metformin HCl and sitagliptin, metformin HCl and a thiazolidinedione (i.e., pioglitazone), and in combination with insulin (with or without other anti-hyperglycemic agents). The medication treatments for Type 2 Diabetes Mellitus (T2DM) include:
- Monotherapy: canagliflozin (INVOKANA)
- Combination therapy:
- canagliflozin with metformin HCl
- canagliflozin with sulfonylurea
- canagliflozin with metformin HCl and sulfonylurea
- canagliflozin with metformin HCl and sitagliptin
- canagliflozin with metformin HCl and a thiazolidinedione (i.e., pioglitazone)
- canagliflozin with insulin (with or without other anti-hyperglycemic agents) 2
From the Research
Medication Treatments for Type 2 Diabetes Mellitus (T2DM)
The following are some of the medication treatments for T2DM:
- Metformin: an oral biguanide that ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production 3
- Sulfonylureas: stimulate insulin secretion, but may cause hypoglycemia or weight gain 3, 4, 5, 6
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors: reduce cardiovascular events in patients with T2DM, particularly those with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease 4, 7
- Glucagon-like peptide 1 receptor agonists (GLP1 RAs): reduce cardiovascular events in patients with T2DM, particularly those with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease 4, 7
- Dipeptidyl peptidase 4 (DPP4) inhibitors: may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin, with less risk of hypoglycemia compared to sulfonylureas 7, 5
- Thiazolidinediones (TZD): may be used as a second-line therapy, but their use is limited due to potential side effects 7
Second-Line Therapy Options
The choice of second-line therapy for T2DM depends on various factors, including cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost. Some clinical guidelines recommend the following second-line therapy options:
- SGLT2 inhibitors or GLP1 RAs for patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease 4
- DPP4 inhibitors, sulfonylureas, or thiazolidinediones for patients without these conditions 4, 7
- Sulfonylureas as the preferred treatment for some types of monogenic diabetes and for T2D patients who may have greater benefit from sulfonylureas based on certain phenotypes and genotypes 6