A comparison of insulin lispro Mix25™ and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan

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Abstract

Objective: To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning and evening postprandial glucose (PPG) control, and on average daily blood-glucose (BG), in patients with Type 2 diabetes who wish to fast during Ramadan. Method: Insulin lispro Mix25 and human insulin 30/70 were compared in an open-label, multicenter, randomised, crossover study involving 151 patients. Each treatment period had a duration of 14 days during which the patients self-monitored their BG before and 2 h after the main meals on any 3 days within the last 5 days of each treatment period. Results: The 2 h PPG excursion following the main evening meal after sunset was significantly lower with insulin lispro Mix25 (3.4±2.9 mmol/l) compared with human insulin 30/70 (4.0±3.2 mmol/l, P=0.007). The evening pre-meal fasting BG values were also lower with insulin lispro Mix25 (7.1±2.2 mmol/l) versus human insulin 30/70 (7.5±2.6 mmol/l, P=0.034). The average daily BG concentration was 9.5±2.4 mmol/l during treatment with insulin lispro Mix25 versus 10.1±2.5 mmol/l with human insulin 30/70 given in identical doses (P=0.004). Conclusion: When compared with human insulin 30/70, treatment of insulin-requiring Type 2 patients with insulin lispro Mix25 during Ramadan resulted in better average daily glycaemia, and better BG control before and after the evening meal. Insulin lispro Mix25 should be considered as a therapeutic option 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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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.

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