Summary

• This information is intended to be a concise summary of representative clinical data; not all available published literature is incorporated into this response.
• INVOKANA is available as 100 mg or 300 mg film-coated tablets for oral administration. The recommended starting dose of INVOKANA is 100 mg once daily, taken before the first meal of the day. In patients tolerating INVOKANA 100 mg once daily who have an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m² or greater and require additional glycemic control, the dose can be increased to 300 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of INVOKANA is recommended.¹

Phase 4 Study

• A randomized, double-blind, placebo-controlled, 26-week, phase 4 study evaluated the efficacy and safety of titrated INVOKANA in patients with type 2 diabetes mellitus on stable combination therapy with maximally or near maximally effective doses of metformin and sitagliptin. Patients received INVOKANA 100 mg once daily during the first 6 weeks, which was then titrated from 100 to 300 mg (or placebo to matching placebo) after certain criteria were met.²

Phase 3 Studies

• The efficacy and safety of INVOKANA was evaluated in several phase 3 studies including core and extension study periods. In most phase 3 studies, INVOKANA was administered at a starting dose of 100 or 300 mg once daily.^3-14

Efficacy

• INVOKANA 100 and 300 mg, used as monotherapy or in combination with other antihyperglycemic regimens, had clinically and statistically significant improvements in HbA1C compared with placebo in core study periods.^{1,3-6,8,10,15}
• In the core plus extension period (up to 52 or 104 weeks), INVOKANA 100 and 300 mg maintained reductions from baseline in HbA1C, FPG, body weight, and systolic blood pressure, with small increases in high-density lipoprotein cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) relative to the comparator.^6,10-14
• In 2 randomized, 52-week, active-controlled studies (study 1, N=1284; study 2, N=755) that included patients randomized to either INVOKANA 100 or 300 mg (as an add-on to either metformin alone [study 1] or metformin + sulfonylurea [study 2]) or sitagliptin 100 mg, INVOKANA 300 mg demonstrated statistical superiority to sitagliptin 100 mg in lowering HbA1C at 52 weeks.^10,16
• In a randomized, double-blind, 104-week study that evaluated INVOKANA (100 and 300 mg) vs glimepiride (6-8 mg; titrated) as an add-on to metformin over a 52-week activecontrolled core period followed by a 52week active-controlled extension (N=1450), both INVOKANA doses demonstrated noninferiority to glimepiride in lowering HbA1C, with INVOKANA 300 mg demonstrating statistical superiority to glimepiride at 52 weeks. Similarly, HbA1C reductions were consistent at week 104, demonstrating the durability of both doses of INVOKANA.^9,13
• The CANVAS Program^17,18(N=10,142) consisted of an integrated analysis of 2 cardiovascular outcome studies namely CANVAS^18-20that consisted of patients randomized 1:1:1 to INVOKANA 100 mg, INVOKANA 300 mg, or placebo and CANVASR^18,21,22that consisted of patients randomized 1:1 to an initial dose of INVOKANA 100 mg or placebo with an optional up titration to INVOKANA 300 mg at week 13 (or anytime thereafter). A statistically significant mean difference in HbA1C was observed for INVOKANA vs placebo (P<0.001).¹⁷

Safety

• Both doses of INVOKANA resulted in higher rates of asymptomatic genital mycotic infections (GMIs), urinary tract infections (UTIs), osmotic diuresis–related adverse events (AEs), and reduced intravascular volume-related AEs. Few events led to study discontinuations.^3-5,7-9,16
• For laboratory parameters, both INVOKANA doses demonstrated decreases from baseline in alanine aminotransferase, gamma-glutamyl transferase, and urate; an increase from baseline in Hb (vs a slight decrease with glimepiride); and higher increases vs placebo or other active treatments in blood urea nitrogen. The decrease in eGFR was larger for patients in the INVOKANA groups than for those in the glimepiride or placebo group; decreases were similar for INVOKANA 300 mg and sitagliptin 100 mg.^3-10,16
• A pooled safety analysis of 4 placebo-controlled studies^4-6,10 evaluating the intensity of GMIs and UTIs was conducted.^23,24

Phase 2 Study

• In a 12-week, phase 2b, dose-ranging study (N=451), all INVOKANA doses (50 mg once daily, 100 mg once daily, 200 mg once daily, 300 mg once daily, and 300 mg twice daily) significantly reduced glycated hemoglobin (HbA1C) and fasting plasma glucose (FPG) compared with placebo. Maximal reductions in HbA1C were seen with 300 mg once daily dosing. The incidence of AEs was similar across treatment groups, except for a non-dose-dependent increase in symptomatic and asymptomatic GMIs in women receiving INVOKANA (P<0.001).²⁵

Additional Reference

• An additional citation identified during literature search is included in the REFERENCES section for your review.²⁶

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 06 August 2024.