Introduction

  • Most Muslim adults with type 2 diabetes (T2D) choose to fast during Ramadan, with >85% fasting for ≥15 days days1-3
  • 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

Population

Adults with T2D treated with iGlarLixi for ≥3 months prior to study start who intended to fast for ≥15 days during Ramadan*

  • 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‡
  • Changes in HbA HbA1c, 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

Baseline characteristics N=420*
Age (years)
≥65 years 		57.1 ± 9.8
101 (24.0)
Female 188 (44.8)
BMI (kg/m2)
Body weight (kg)		 30.9 ± 5.3
86.5 ± 14.9
Diabetes duration (years)
≥10 years		 12.1 ± 6.4
246 (58.6)
HbA1c(%) pre-Ramadan period 8.2 ± 1.2
FPG (mg/dL) pre-Ramadan period 140 ± 38
Duration of iGlarLixi treatment (months months†)
iGlarLixi started in insulin-naïve ve participants
iGlarLixi started after previous insulin treatment		 6.2 ± 4.2
174 (41.9)
241 (58.1)
Concomitant non-insulin antihyperglycaemic treatment pre-Ramadan period period ‡
Biguanides
Sulfonylureas
SGLT-2 inhibitors
Thiazolidinedione
Glinides
DPP-4 inhibitors		 359 (85.5)
234 (55.7)
188 (44.8)
173 (41.2)
18 (4.3)
7 (1.7)
1 (0.2)

*Eligible population; †Up to signing of informed consent form; ‡A participant can be included in several categories Data are mean ± SD or n (%)
BMI, body mass index; DPP-4, dipeptidyl peptidase-4; FPG, fasting plasma glucose; SD, standard deviation; SGLT-2, sodium-glucose co-transporter-2

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)

Eligible population. Last month pre-Ramadan and first month post-Ramadan

Secondary endpoints

  • HbA1c , FPG and body weight all improved from pre-to post-Ramadan (Figure3)
  • The proportion of participants reaching HbA1c <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)

CI, confidence interval; FPG, fasting plasma glucose, SD, standard deviation

Adverse events

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

Table 2: Adverse events

Adverse events N=428*
Any 20 (4.7)
Any serious AE 0 (0.0)
Any treatment treatment-related AE 0 (0.0)
Any AE leading to permanent treatment discontinuation 1 (0.2)
Any AE leading to death 0 (0.0)

*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

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 HbA1c 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

    1. International Diabetes Federation, Diabetes and Ramadan 2021
    2. Babineaux SM et al. Diabetic Med 2015;32:819 819–28
    3. Hassanein M et al. Diab Res Clin Pract 2019;151:275 275–84
    4. Hassanein M et al. Diab Res Clin Pract 2019;150:331 331–41

MAT-BH-2200285/V2/MAR2024