From the Guidelines
A third medication that can be added to metformin and Trulicity (dulaglutide) for diabetes management is an SGLT-2 inhibitor such as empagliflozin (Jardiance), dapagliflozin (Farxiga), or canagliflozin (Invokana). These medications work through a different mechanism than metformin (which decreases glucose production in the liver) and Trulicity (a GLP-1 receptor agonist that increases insulin secretion) 1. SGLT-2 inhibitors reduce blood glucose by preventing kidney reabsorption of glucose, causing it to be excreted in urine. This triple therapy approach can be particularly beneficial for patients who haven't achieved their glycemic targets with dual therapy.
Key Considerations
- SGLT-2 inhibitors offer additional benefits beyond glucose control, including weight loss, blood pressure reduction, and cardiovascular and kidney protection 2.
- The typical starting dose for empagliflozin is 10 mg once daily, dapagliflozin 5-10 mg once daily, or canagliflozin 100 mg once daily.
- Patients should be monitored for side effects including genital mycotic infections, urinary tract infections, and volume depletion, especially in elderly patients or those on diuretics.
Patient Selection
- For patients with established ASCVD or indicators of high ASCVD risk, heart failure, or CKD, an SGLT2 inhibitor or GLP-1 RA with demonstrated CVD benefit is recommended as part of the glucose-lowering regimen independent of A1C, independent of metformin use 1.
- The choice of medication added to metformin is based on the clinical characteristics of the patient and their preferences, including the presence of established ASCVD or indicators of high ASCVD risk, heart failure, CKD, other comorbidities, and risk for specific adverse drug effects, as well as safety, tolerability, and cost 1.
From the FDA Drug Label
In Combination with Metformin HCl + Sulfonylurea (26 weeks) Placebo + Metformin HCl + Sulfonylurea (N=156) INVOKANA 100 mg + Metformin HCl + Sulfonylurea (N=157) INVOKANA 300 mg + Metformin HCl + Sulfonylurea (N=156) Overall [N (%)]24 (15.4)43 (27.4)47 (30.1) In Combination with Metformin HCl + Pioglitazone (26 weeks) Placebo + Metformin HCl + Pioglitazone (N=115) INVOKANA 100 mg + Metformin HCl + Pioglitazone (N=113) INVOKANA 300 mg + Metformin HCl + Pioglitazone (N=114) Overall [N (%)]3 (2.6)3 (2.7)6 (5.3)
A suitable third medication to add to a diabetes treatment regimen consisting of metformin and Trulicity (dulaglutide) could be canagliflozin (INVOKANA), as it has been studied in combination with metformin and other medications, including sulfonylureas and pioglitazone. However, it is essential to consider the potential risks and benefits, including the increased risk of hypoglycemia and genital mycotic infections. The decision to add canagliflozin should be made on a case-by-case basis, taking into account the individual patient's needs and medical history 3.
- Key considerations:
- Monitor for signs of hypoglycemia and genital mycotic infections
- Adjust the dose of concomitant medications as needed to minimize the risk of hypoglycemia
- Consider the potential benefits of canagliflozin, including improved glycemic control and weight loss.
From the Research
Suitable Third Medication for Diabetes Treatment Regimen
To determine a suitable third medication to add to a diabetes treatment regimen consisting of metformin and Trulicity (dulaglutide), we can consider the following options:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which have been shown to be effective in reducing blood glucose levels and have added benefits in patients with obesity, renal disease, heart failure, and cardiovascular disease 4
- Dipeptidyl peptidase-4 (DPP-4) inhibitors, which have been demonstrated to have similar results to metformin and SGLT2 inhibitors in preventing worsening cardiac outcomes 5
- Other glucagon-like peptide-1 (GLP-1) receptor agonists, which have been shown to have significant positive effects on glycemia and have added benefits in patients with obesity, renal disease, heart failure, and cardiovascular disease 5
Rationale for Choosing a Third Medication
The choice of a third medication should be based on the individual patient's needs and medical history. For example:
- If the patient has a history of cardiovascular or renal disease, an SGLT2 inhibitor may be a suitable choice 4
- If the patient has obesity or needs further hemoglobin A1c reduction, an SGLT2 inhibitor or a DPP-4 inhibitor may be a suitable choice 4, 5
- If the patient is already taking a GLP-1 receptor agonist (such as Trulicity), a different class of medication may be preferred to minimize potential interactions or side effects 5
Evidence for Combination Therapy
Studies have shown that combination therapy with metformin and an SGLT2 inhibitor can provide better glycemic control than metformin or SGLT2 inhibitor monotherapy 6, 7. Additionally, combination therapy with metformin and a GLP-1 receptor agonist (such as Trulicity) has been shown to be effective in reducing blood glucose levels and improving cardiovascular outcomes 8, 5.