iGlarLixi Enables Safe Ramadan Fasting for Most T2D Patients

Introduction

• Most Muslim adults with type 2 diabetes (T2D) choose to fast during Ramadan, with >85% fasting for ≥15 days days^1-3
• The incidence of hypoglycaemia increases during Ramadan compared with prepre-Ramadan, and adjustments to diabetes treatment must be considered to prevent severe hypoglycaemia³
• Separate administration of basal insulin + the glucagon glucagon-like peptide peptide-1 receptor agonist, lixisenatide, has been shown to demonstrate lower risk of hypoglycaemia during Ramadan versus sulfonylureas + lixisenatide lixisenatide⁴
• In the SoliRam study, the safety and effectiveness of iGlarLixi (a fixed fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide) were evaluated in adults with T2D during Ramadan

Objective

To assess the safety and effectiveness of iGlarLixi in people with T2D fasting during Ramadan

Study design

SoliRam was a multicentre, multinational, prospective, single-arm, real-world observational study during Ramadan 2020 (Wave 1) and 2021 (Wave 2) (Figure 1)

Figure 1: SoliRam study design and endpoints

Primary endpoint

• Proportion of participants experiencing at least one documented (<70 mg/dL [<3.9 mmol/L]) and/or severe symptomatic hypoglycaemia event during pre pre-Ramadan, Ramadan, post post-Ramadan and the whole study period period^‡

Secondary endpoints

• Changes in HbA HbA_1c, FPG and body weight from pre-to post post-Ramadan
• Changes in iGlarLixi and other non-insulin antihyperglycaemic treatment
• AEs and serious AEs

*Participants who entered Wave 1 were not included in Wave 2; ^†Participant follow follow-up was preferably 1 month after the end of Ramadan; ^‡Whole study period: pre-Ramadan to post-Ramadan.

During the study, iGlarLixi and concomitant treatments were adjusted by physicians as per routine practice AE, adverse event; DAR, Diabetes and Ramadan; FPG, fasting plasma glucose; IDF, International Diabetes Federation; iGlarLixi, a fixed fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, T2D, type 2 diabetes

• Participants were enrolled from Egypt, Indonesia, Israel, Kuwait, Lebanon, Malaysia, Philippines, Saudi Arabia and the United Arab Emirates
• This analysis presents descriptive statistics from the entire SoliRam study

Results

Participant baseline characteristics

• Overall, 420 people with T2D were eligible. Baseline characteristics are presented in Table 1
• In total, 409 participants were assessed during the Ramadan period

Table 1: Participant baseline characteristics

*Eligible population; †Up to signing of informed consent form; ^‡A participant can be included in several categories Data are mean ± SD or n (%)

Antihyperglycaemic therapies during Ramadan

• At the selection visit (n=420), iGlarLixi injection time was at breakfast, lunch or dinner for 41.2%, 36.2% and 22.6% of participants, respectively
• During Ramadan most participants (88.8%) took iGlarLixi at Iftar
• iGlarLixi mean ± standard deviation (SD) daily dose was 25.8 ± 11.0 U pre-Ramadan and 24.8 ± 9.9 U during Ramadan
• Minimal adjustments were made to antihyperglycaemic therapies from pre-Ramadan to during Ramadan. Oral antihyperglycaemic drugs were used by 83.8% of participants during Ramadan (54.5% biguanides, 43.8% sulfonylureas and 40.5% sodium sodium-glucose co-transporter-2 [SGLT SGLT-2] inhibitors)

Fasting during Ramadan

• Most participants (96.9%) were able to fast for ≥25 days (mean ± SD, 28.8 ± 2.7 days), with 92.4% not breaking their fast during the whole Ramadan period
• Of the 31 (7.6%) participants who did break their fast, four (12.9%) reported hypoglycaemia as the reason

Hypoglycaemia during Ramadan

• Primary endpoint: The number of participants reporting ≥1 severe and/or documented symptomatic hypoglycaemia events <70 mg/dL (<3.9 mmol/L) was low throughout the whole study ( Figure 2A)
• The number of participants reporting ≥1 severe and/or documented symptomatic hypoglycaemia events <54 mg/dL (<3.0 mmol/L) was also low throughout the study ( Figure 2B)
• No severe hypoglycaemia events occurred during the whole study period

Figure 2: Incidence of documented symptomatic and/or severe hypoglycaemia (A) <70 mg/dL (<3.9 mmol/L), (B) <54 mg/dL (<3.0 mmol/L)

Secondary endpoints

• HbA_1c , FPG and body weight all improved from pre-to post-Ramadan (Figure3)
• The proportion of participants reaching HbA_1c <7 % increased from 7.9% pre-Ramadan to 28.6% post-Ramadan (evaluable population, n=343)

Figure 3: Changes in (A) HbA1c, (B) FPG and (C) body weight between pre-and post-Ramadan periods

Evaluable population: HbA1c, N=343; FPG, N=334; Eligible population: body weight, N=356 (post-Ramadan observed data)

Adverse events

• Overall, 4.7% of participants (n=20) reported adverse events (AEs) of any cause ( Table 2)

Table 2: Adverse events

*Included population. Data are n (%) AE, adverse event

• Gastrointestinal AEs were reported by four (0.9%) participants
• The AE leading to discontinuation was asthenia, and treatment was stopped by the participant without physician advice

Incidence of other Hypoglycaemia events

Incidence of documented (<54 mg/dL [<3.0 mmol/L]) symptomatic and/or severe hypoglycaemia events

Eligible population. n=410 Last month Pre-Ramadan, n=394 Ramadan and n=380 First month Post-Ramadan Poster presentation EDEC 2022, Mohamed Hassanein et al, EDEC2022 (edec-uae.com) last accessed 27th February 2022.

Changes in FPG

Improvements were also observed in FPG

FPG n=334 for both Pre- and post-Ramadan; Body weight n=406 (Pre-Ramadan), n=356 (Post-Ramadan) CI, confidence interval; FPG, fasting plasma glucose; SD, standard deviation.

Discussion

• In this real real-world study of adults with T2D from diverse regions fasting during Ramadan, over 90% of participants treated with iGlarLixi were able to fast for the entire month of Ramadan, with few participants experiencing severe and/or documented (<70 mg/dL [<3.9 mmol/L]) symptomatic hypoglycaemia
• Adjustments to antihyperglycaemic regimens were minimal and HbA_1c levels did not increase over Ramadan
• No participants experienced severe hypoglycaemia

Conclusion

iGlarLixi may be a suitable and effective treatment option for people with T2D who intend to fast during Ramadan