Invokamet is a fixed-dose combination oral tablet that pairs canagliflozin (an SGLT2 inhibitor) with metformin in a single twice-daily pill. Invokamet XR offers once-daily extended-release dosing. The combination delivers A1C reduction of 1.5 to 2.5 percent, modest weight loss, and the cardiovascular and kidney protection benefits demonstrated by canagliflozin in the CANVAS and CREDENCE trials. Historical amputation and fracture signals have shaped its prescribing pattern, though the FDA removed the boxed amputation warning in 2020.
What Invokamet Contains
Invokamet is manufactured by Janssen (a Johnson and Johnson subsidiary). Active ingredients:
- Canagliflozin — an SGLT2 inhibitor that blocks glucose reabsorption in the proximal tubule of the kidney, causing approximately 80 to 119 grams of glucose to be excreted in urine daily (a slightly higher amount than empagliflozin or dapagliflozin). Effects include glucose lowering, weight loss of 2 to 4 kg, systolic blood pressure reduction of 4 to 6 mmHg, and demonstrated cardiovascular and kidney protection.
- Metformin hydrochloride — a biguanide that decreases hepatic glucose production, improves insulin sensitivity, and slows intestinal glucose absorption. Foundational first-line type 2 diabetes therapy.
Available Strengths
| Strength | Canagliflozin | Metformin | Frequency |
|---|---|---|---|
| 50/500 mg (IR) | 50 mg | 500 mg | Twice daily |
| 50/1000 mg (IR) | 50 mg | 1,000 mg | Twice daily |
| 150/500 mg (IR) | 150 mg | 500 mg | Twice daily |
| 150/1000 mg (IR) | 150 mg | 1,000 mg | Twice daily |
| 50/500 to 300/2000 mg (XR) | 50 to 300 mg total daily | 500 to 2000 mg total daily | Once daily |
Maximum daily dose is canagliflozin 300 mg plus metformin 2,000 mg.
Dosing Instructions
- Invokamet (immediate-release): take one tablet twice daily, with the first meal of the day for the morning dose. Taking before the first meal helps maximize the postprandial glucose effect of canagliflozin.
- Invokamet XR: take once daily with the morning meal.
- Swallow whole — do not crush, split, or chew (especially the XR formulation).
- If a dose is missed, take it as soon as remembered with food the same day. Skip if it is close to the next dose.
- Maintain adequate hydration throughout the day.
Who Invokamet Is For
Invokamet is approved for adults with type 2 diabetes as an adjunct to diet and exercise. Common scenarios:
- A1C remains above goal despite metformin monotherapy
- Already taking canagliflozin and metformin separately and want to consolidate
- Type 2 diabetes with chronic kidney disease (diabetic nephropathy) — CREDENCE benefit
- Cardiovascular disease or elevated cardiovascular risk
It is generally avoided in patients with prior lower-limb amputation, active foot ulcers, peripheral arterial disease, or significant fracture risk. It is not approved for type 1 diabetes, diabetic ketoacidosis, or pediatric patients.
How Well Invokamet Works
Clinical data from the component drugs and combination studies show:
- A1C reduction: approximately 1.5 to 2.5 percent in patients with poorly controlled type 2 diabetes.
- Weight loss: 2 to 4 kg over 24 to 52 weeks, primarily from canagliflozin’s caloric loss.
- Blood pressure: systolic reduction of 4 to 6 mmHg.
- Cardiovascular benefit: CANVAS program (CANVAS and CANVAS-R, 10,142 patients) showed a 14 percent relative reduction in major adverse cardiovascular events in patients with type 2 diabetes and high cardiovascular risk.
- Kidney protection: CREDENCE trial demonstrated a 30 percent reduction in the composite endpoint of doubling of serum creatinine, end-stage kidney disease, or renal/cardiovascular death in patients with type 2 diabetes and chronic kidney disease.
For context on what these A1C reductions mean clinically, see our explainer on A1C levels and treatment targets.
Side Effects
| Side Effect | Source | Approximate Frequency |
|---|---|---|
| Genital yeast infections (women) | Canagliflozin | 10 to 12 percent |
| Genital yeast infections (men) | Canagliflozin | 4 to 6 percent |
| Urinary tract infections | Canagliflozin | 5 to 8 percent |
| Increased urination, thirst | Canagliflozin | 4 to 6 percent |
| Diarrhea, nausea, abdominal pain | Metformin | 10 to 25 percent (often transient) |
| Volume depletion, hypotension | Canagliflozin | 2 to 4 percent |
| Hyperkalemia | Canagliflozin (in CKD) | 3 to 5 percent |
| Lower-limb amputation | Canagliflozin (CANVAS finding) | ~6 vs 3 per 1,000 patient-years |
| Bone fractures | Canagliflozin (CANVAS finding) | ~15 vs 11 per 1,000 patient-years |
| Euglycemic DKA | Canagliflozin | Rare (less than 0.1 percent) |
| Lactic acidosis | Metformin | Very rare (3 to 10 per 100,000) |
| Fournier’s gangrene | SGLT2 class | Extremely rare |
| Vitamin B12 deficiency | Metformin (long-term) | 5 to 10 percent at 5+ years |
Contraindications and Warnings
- eGFR less than 30 mL/min/1.73 m squared: contraindicated due to metformin lactic acidosis risk; canagliflozin alone may be continued with caution.
- eGFR 30 to 45: existing users may continue cautiously; do not initiate.
- Prior lower-limb amputation: use cautiously or avoid.
- Active foot ulcers, peripheral arterial disease, or diabetic neuropathy: screen carefully; consider an alternative SGLT2 inhibitor.
- Active diabetic ketoacidosis or type 1 diabetes.
- Severe hepatic impairment, acute or chronic metabolic acidosis, or chronic alcoholism.
- History of recurrent UTIs or genital infections: use cautiously.
- Hold around iodinated contrast and major surgery (48 hours before and after).
- Pregnancy: not recommended in second or third trimester.
Drug Interactions
- UGT inducers (rifampin, phenytoin, phenobarbital): reduce canagliflozin levels; may need dose adjustment.
- Digoxin: canagliflozin can increase digoxin exposure — monitor levels.
- Cationic drugs (cimetidine, dolutegravir): can increase metformin levels.
- Loop and thiazide diuretics: additive volume depletion.
- Insulin and sulfonylureas: increase hypoglycemia risk; doses may need reduction.
- Iodinated contrast: hold 48 hours before and after.
- Alcohol: increases lactic acidosis and hypoglycemia risk.
Cost and Insurance
Invokamet retails for approximately $550 to $700 per month at U.S. pharmacies. Janssen’s manufacturer savings card can reduce out-of-pocket costs for commercially insured patients to as little as $0 per month for up to 12 months, with annual savings limits. Medicare and Medicaid patients are not eligible for the savings card but may qualify for Janssen’s patient assistance program based on income.
Storage
- Store at controlled room temperature 68 to 77 degrees F (20 to 25 degrees C).
- Keep in original blister or bottle until use.
- Protect from moisture and heat.
- Do not crush, split, or chew tablets, especially the XR formulation.
Invokamet vs Other SGLT2 + Metformin Combinations
| Feature | Invokamet | Synjardy | Xigduo XR |
|---|---|---|---|
| SGLT2 component | Canagliflozin | Empagliflozin | Dapagliflozin |
| CV outcomes trial | CANVAS | EMPA-REG | DECLARE-TIMI 58 |
| Kidney outcomes trial | CREDENCE | EMPA-KIDNEY | DAPA-CKD |
| Heart failure trial | None dedicated | EMPEROR-Reduced/Preserved | DAPA-HF/DELIVER |
| Amputation signal | Yes (boxed removed 2020) | No | No |
| Fracture signal | Yes | No | No |
| Dosing | Twice daily IR or once XR | Twice daily IR or once XR | Once daily (XR only) |
Although Invokamet has strong cardiovascular and kidney outcome data, the historical amputation and fracture signals have shifted clinical preference toward empagliflozin and dapagliflozin-based combinations for many prescribers. CREDENCE remains a unique strength for canagliflozin in diabetic CKD, particularly in patients without significant amputation risk.
The Amputation Signal in Context
The CANVAS program found lower-limb amputation occurred at 6.3 per 1,000 patient-years on canagliflozin versus 3.4 per 1,000 patient-years on placebo. Risk was concentrated in patients with prior amputation, peripheral arterial disease, neuropathy, or active foot ulcers. The CREDENCE trial of canagliflozin in diabetic CKD did not show an increased amputation risk, and a 2019 meta-analysis of subsequent trials did not confirm the CANVAS signal — leading the FDA to remove the boxed warning in August 2020. Clinicians still screen carefully and monitor feet during therapy, but the absolute risk is now considered modest in carefully selected patients.
Place in Modern Type 2 Diabetes Care
ADA Standards of Care 2024 recommend SGLT2 inhibitors as preferred second-line agents in patients with type 2 diabetes plus established cardiovascular disease, heart failure, or chronic kidney disease — regardless of A1C. Invokamet remains a reasonable option for patients with diabetic nephropathy who benefit from canagliflozin’s strong CREDENCE evidence and who do not have amputation or fracture risk factors. For broader treatment context, see our type 2 diabetes treatment options.
Practical Considerations for Patients
- Take Invokamet IR with the first meal of the day for the morning dose; XR with the morning meal.
- Drink at least 8 glasses of water daily.
- Practice good genital hygiene to reduce yeast infection risk; uncircumcised men should clean the foreskin daily.
- Inspect feet daily for blisters, sores, redness, or temperature changes — call your clinician for any new lesion.
- Wear well-fitting shoes and avoid going barefoot.
- Discuss bone health with your clinician, including calcium and vitamin D intake and weight-bearing exercise to mitigate fracture risk.
- Inform any new clinician about Invokamet before surgery, contrast imaging, or new prescriptions.
- Monitor kidney function and electrolytes at least annually.
Invokamet and Weight
Patients typically lose 2 to 4 kg over 6 to 12 months, primarily from canagliflozin’s caloric loss through urinary glucose excretion. Weight loss tends to plateau after the first year. For larger weight loss, GLP-1 receptor agonists like semaglutide or tirzepatide are more effective — see our pages on Wegovy vs Ozempic for alternatives.
Invokamet in Prediabetes
Invokamet is not approved for prediabetes. SGLT2 inhibitors are reserved for type 2 diabetes, and metformin alone is sometimes used off-label for high-risk prediabetic individuals. Lifestyle modification, weight loss, and physical activity remain first-line. See our discussion of whether prediabetes is reversible for context.
The Bottom Line
Invokamet combines canagliflozin and metformin in a single twice-daily tablet (or once-daily Invokamet XR) for adults with type 2 diabetes. Combined A1C reduction of 1.5 to 2.5 percent comes with modest weight loss, blood pressure reduction, and the cardiovascular and kidney protection demonstrated in CANVAS and CREDENCE. Canagliflozin’s historical amputation and fracture signals from CANVAS have shifted prescribing toward empagliflozin and dapagliflozin combinations in many clinics, though the boxed amputation warning was removed by the FDA in 2020. Common side effects include genital infections, urinary tract infections, and mild GI symptoms. Talk to your clinician about whether Invokamet’s strong CREDENCE kidney evidence fits your situation, especially if you have diabetic nephropathy and no amputation or significant fracture risk factors.
