A comparison of insulin lispro Mix25™ and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan
Introduction
Ramadan is the ninth month of the Muslim calendar and is a fundamental principle of Islam strictly observed by more than one billion Muslims worldwide. Although patients with serious illnesses, including those with diabetes mellitus, are exempt from fasting during the holy month, most prefer to do so [1]. Depending on the geographical area and time of year when Ramadan occurs, fasting can last up to 11–19 h per day. As food or drink can only be taken between sunset (Iftar) and sunrise (Sahur), patients treated with insulin have difficulty maintaining glucose control [2]. The risk of hyperglycaemia escalates as a result of increased caloric intake per meal due to the reduced number of meals and the reluctance of Ramadan followers to take oral and injected medication during the fasting period. As a result, the optimal timing of regular human insulin formulations is not commonly followed by patients so that, insulin injections are often administered immediately before the meal. These changes in dietary habits can result in extreme postprandial glucose (PPG) excursions which have been shown to be associated with increased risk of chronic complications, including cardiovascular events [3], [4], [5], [6].
The pharmacokinetic (PK) profile of standard insulin formulations may be partially responsible for hyperglycaemia and hypoglycaemic events as their usage is associated with non-physiologic hypoinsulinemia or hyperinsulinemia if a major discrepancy between insulin reabsorption and net glucose transfer in and out of circulation occurs. Humalog® Mix25™ (Mix25; known as Humalog® Mix75/25™ in the US), is a pre-mixed insulin containing 25% insulin lispro and 75% neutral protamine lispro (NPL, an intermediate-acting insulin). The insulin lispro component of Mix25 has a speedy onset (15 min) and a short duration (3–5 h) activity, so that its PK profile closely resembles the normal pattern of insulin secretion [7]. In this clinical situation, these PK characteristics result in improved metabolic control in the postprandial period [8], [9], [11], and are associated with reduced risk of hypoglycaemia, particularly in the late postprandial period and during the night when compared with human pre-mixed insulin 30/70 [8], [11]. In this study, we compared the effects of insulin lispro Mix25 (lispro Mix25) and human insulin 30/70 (insulin 30/70) on the daily BG profiles in insulin-requiring patients with Type 2 diabetes who wished to fast during Ramadan. The primary objective was to assess postprandial BG control with these insulin preparations. During the lead-in and follow up period data related to hypoglycaemic events were also collected and analysed at endpoint.
Section snippets
Patients
One hundred fifty-one patients with Type 2 diabetes, from 13 study sites located in seven countries (India, Pakistan, Malaysia, Singapore, Egypt, Morocco, and South Africa) participated in this trial. The main eligibility criteria included: (a) satisfying the diagnostic criteria for Type 2 diabetes according to the World Health Organisation [12]; (b) being treated with conventional insulin therapy (regular Hagedorn (NPH) insulin in twice daily regimen, with or without metformin) for at least 2
Daily BG profile
The overall glycaemia, measured as the average of the four BG values, was significantly lower with lispro Mix25 (9.5±2.4 mmol/l) when compared with human insulin 30/70 (10.1±2.5 mmol/l, P=0.004; see Table 2). The greatest difference between the two regimens was observed before dinner (evening pre-meal BG with lispro Mix25 was 7.1±2.2 vs. 7.5±2.6 mmol/l for insulin 30/70; adjusted P-value=0.034) and 2 h after dinner (for lispro Mix25 was 10.5±3.2 mmol/l and for human insulin 30/70 11.6±3.4
Discussion
The metabolic effect of two insulin formulations with different PK and pharmacodynamics (PD) profiles during the holy month of Ramadan was evaluated. Patients with diabetes experience a number of changes during that period, including the need to change the timing of their meals and insulin doses and qualitative changes in the composition of their meals toward increased carbohydrates and fat content. Results of this study indicate that lispro Mix25 is associated with lower average BG
Conclusions
In this study, treatment of Type 2 diabetes with lispro Mix25 was associated with lower average daily glycaemia during Ramadan when compared with a regimen with insulin 30/70. The main effect of Mix25 was observed on BG levels just before and 2 h after the evening meal. Both regimens were well tolerated and did not increase the risk of hypoglycaemia.
Acknowledgements
The authors would like to acknowledge the contributions of the Ramadan study group.
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Cited by (73)
Ramadan fasting in insulin-treated patients is associated with potentially unfavourable changes in glucose metrics: A flash glucose monitoring (FGM) study
2021, Diabetes Research and Clinical PracticeCitation Excerpt :Mitigating the risk of hypoglycaemia is one of the priorities for insulin-treated patients with diabetes, who decide to fast, and their treating healthcare professionals. Typical changes in therapy in the context of the Ramadan fast range from judicious use of intermediate or long-acting insulin preparations plus a short-acting insulin administered before meals [26,27] or use of a rapid-acting insulin analogue instead of regular human insulin before meals to reduce hypoglycemia and postprandial glucose excursions [28,29]. Guidelines also suggest daily doses of short-acting insulin secretagogues may be reduced or redistributed to two doses during Ramadan according to meal size [30].
The frequency of major complications among fasting people with diabetes according to risk categories of IDF-DAR guidelines 2016
2020, Clinical Epidemiology and Global HealthA systematic review on the safety of Ramadan fasting in high-risk patients with Diabetes
2020, Diabetes Research and Clinical PracticeThe South Asian Health Foundation (UK) guidelines for managing diabetes during Ramadan
2020, Diabetes Research and Clinical PracticeImpact of optimum diabetes care on the safety of fasting in Ramadan in adult patients with type 2 diabetes mellitus on insulin therapy
2019, Diabetes Research and Clinical PracticeCitation Excerpt :They concluded that the use of Levemir and NovoMix 70 was non-inferior to standard care and was associated with less adverse events [12]. The rest of the studies compared low dose versus high dose premixed insulins [9–11]. Hui E et al. have shown a significant reduction in HbA1c of 0.48% (p = 0.0001) with the use of premixed insulin 50%, whereas low dose combination was associated with an increase in HbA1c of 0.28% [10].
Diabetes Canada Position Statement for People With Types 1 and 2 Diabetes Who Fast During Ramadan
2019, Canadian Journal of DiabetesCitation Excerpt :The evening premeal fasting and the 2-h postprandial excursion after the sunset meal were significantly lower with insulin lispro Mix 25 compared to insulin 30/70. There was no difference in hypoglycemia between the 2 groups (30). Another observational study switching the evening dose of human insulin 30/70 twice daily to lispro Mix 50 in one half of the participants 2 weeks before Ramadan found no significant reduction in hypoglycemia (31).
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Egypt: Hussien El Damassy, Mohamed Abdel Maboud, Ain Shams University, Cairo, Egypt; Megahed Aboul Magd, Mansoura University, Mansoura, Egypt; Abdel Raouf Rashwan, Zagazig University, Sharkia, Egypt. India: Aqeel H. Malbari, Mahendra H. Patel, Chowpatty Medical Center, Mumbai, India; Hasnain L. Patel, Habib Hospital, Mumbai, India; Altaf L. Patel, J.J. Hospital Mumbai, India; Jamal Ahmad, Anand Koppad, Nidhi Shukla, J.N. Medical College, Aligarh Muslim University, Aligarh, India. Malaysia: Rokiah Pendek, Cheong Guan Ooi, Zainab Abu Kassim, Siew Pheng Chan, Fen Lee Hew, Ikram Shah Ismail, University Hospital, Kuala Lumpur, Malaysia; Mafauzy Mohamed, Wan Mohamad Wan Bebakar, Malik Mumtaz, Universiti Sains Malaysia, Kelantan, Malaysia. Morocco: Mohammed Reida Ababou, University Hospital Ibn Rochd, Casablanca, Morocco. Pakistan: Javed Akram, Shahzad Sarwar, Akram Medical Complex, Lahore, Pakistan; Abdul Basit, Muhammad Qamar Masood, Muhammad Zafar Iqbal Hydrie, Baqai Institute of Diabetes and Endocrinology, Karachi, Pakistan; Abdul Jabbar, Fatirna Hussain, The Aga Khan University, Karachi, Pakistan. Singapore: Chung Horn Lee, Yuan Tud Chen, Shu Chuan Vanessa Au, Changi General Hospital, Singapore, Singapore. South Africa: N.S. Levitt, Steven Grant Soule, Groote Schuur Hospital, Cape Town, South Africa. Egypt: Amr A. Hamid Saleh, Eli Lilly and Company. India: Renuka Marwah, Ritika Bajaj, Eli Lilly and Company. Pakistan: Asim Awan, Eli Lilly and Company. South Africa: Laudi Gerber, Petrus Lodewyk Du Toit, Eli Lilly and Company.