SUMMARY  

• In phase 3 trials, INVOKANA was not studied specifically in patients who were not taking anything by mouth/nil per os (NPO) or were fasting.
• There are limited data from 3 studies assessing the safety of INVOKANA in type 2 diabetes mellitus (T2DM) patients who fasted during Ramadan.^1-3
• No specific recommendations are available at this time with regards to administration and timing of INVOKANA in patients who are NPO or fasting.
• Please refer to your institutional/clinical practice guidelines and local labeling and use your clinical judgment to determine appropriate use of INVOKANA in NPO or fasting patients.

CLINICAL DATA

Observational Studies

Bashier et al (2018)¹ conducted a 2-center, prospective study in adults with T2DM who fasted during the month of Ramadan in Dubai, to assess the safety of sodium-glucose cotransporter inhibitors (SGLT2i) (INVOKANA 100 mg or dapagliflozin 10 mg), including hypoglycemia and dehydration (N=417). Secondary outcomes included: change in body weight, A1c, lipid profile, and creatinine.

• Laboratory data were collected before and after Ramadan.
• Hypoglycemic events occurred in 27% of patients (n=113) and confirmed via glucometer in 78 patients.
  • Hypoglycemic events were significantly more frequent in patients on concomitant insulin than those on other oral antihyperglycemic agents (AHAs).
• Symptoms of dehydration occurred in 9.3% of patients and more frequently in patients on concomitant insulin than those on other oral AHAs (39 vs 25 patients, respectively).
• Reductions in A1c and weight were statistically significant by the end of Ramadan. There were no significant changes in lipids or creatinine levels by the end of the study.

Hassanein et al (2017)² conducted a multicenter, open-label, observational study of patients who fasted during the month of Ramadan in the Middle East (Kuwait, Lebanon, and United Arab Emirates) to evaluate tolerability of INVOKANA in combination with metformin and with or without a dipeptidyl peptidase-4 (DPP-4) inhibitor compared to a sulfonylurea in T2DM patients (N=321).

• The primary endpoint was the proportion of patients with ≥1 hypoglycemia episode (including dizziness, visual blurring, palpitations, nausea, sweating, confusion, tremor, or intense hunger), as reported in the patient diary.
• Treatment adherence in both groups was high with no missed doses reported in 98.8% of the INVOKANA group and 96.2% of the sulfonylurea group. The number of missed fasting days was low in both groups with no missed fasting days being reported in 82.1% of the INVOKANA group and 78% of the sulfonylurea group.
• Symptomatic hypoglycemia was noted in 3.7% (n=6) of INVOKANA-treated patients vs 13.2% (n=21) of sulfonylurea-treated patients.
• Volume depletion events occurred more often in the INVOKANA-treated patients (16.1%, n=26) vs sulfonylurea-treated patients (5%, n=8), with the majority of events reported as symptoms of dehydration.
• The osmotic diuresis-related event of thirst was reported in 6.2% (n=10) of INVOKANA-treated patients. No other osmotic diuresis-related events were reported (including pollakiuria, polyuria, or polydipsia).
• Adverse events (AE) were similar in both groups and no serious AEs were reported.

Eid et al (2021)³ conducted an observational cohort study of adults with T2DM who fasted during Ramadan (April 2019-July 2019) in Egypt. The objective was to evaluate the efficacy, safety, and tolerability of SGLT2i (empagliflozin 25 mg, dapagliflozin 10 mg or INVOKANA 300 mg) in combination with metformin compared to sulfonylureas (glimepiride 1–6 mg/day or gliclazide MR 60–120 mg/day) in combination with metformin.

• The primary outcomes were hypoglycemic episodes (symptomatic, documented [fasting blood glucose < 70 mg/dl] and severe [episodes in which patients required assistance from another person or that resulted in seizure or loss of consciousness]), volume depletion episodes, and the number of days that the patient took early fasting breaks or missed days of fasting. Secondary endpoints were changes in BMI and HbA1c after Ramadan.
• 94 T2DM participants were included in this study.
  • 51 participants in the metformin + sulfonylurea group.
  • 43 participants in the metformin + SGLT2i group.
• Patients in the SGLT2i group experienced significantly fewer symptomatic (9.3% vs 35.3%, P=0.003) and documented (7.0% vs 25.5%, P=0.017) hypoglycemic episodes in comparison to the sulfonylurea group.
• There were no significant differences between both groups regarding the frequency of patients with volume depletion episodes (5.9% vs 16.3%, P=0.1).
• There were no significant differences between both groups regarding the frequency of patients with early fasting break (11.8% vs 9.3%, P=0.7) or missed fasting (3.9% vs 2.3%, P=0.66).
• Levels of BMI and HbA1c after Ramadan fasting showed a nonsignificant difference between the SGLT2i group and sulfonylurea group (P=0.66, P=0.22 respectively).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 29 March 2023.