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Opinion Article | DOI: https://doi.org/10.31579/2640-1045/152
Advisor doctor and expert trainer The National Training and Development Center and Baghdad Medical City
*Corresponding Author: Aamir Jalal Al-Mosawi, Advisor doctor and expert trainer The National Training and Development Center and Baghdad Medical City
Citation: Aamir Jalal Al-Mosawi, (2023), The use of Oral Anti-Diabetic Medications in Diabetes Mellitus type 1: An Educational Article and Expert Opinion, J. Endocrinology and Disorders, 7(6): DOI:10.31579/2640-1045/152
Copyright: © 2023, Aamir Jalal Al-Mosawi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 18 August 2023 | Accepted: 28 August 2023 | Published: 11 September 2023
Keywords: diabetes mellitus type 1; oral anti-diabetics; expert opinion
Diabetes mellitus type 1 is lifelong condition resulting from failure of production of insulin because of the loss of pancreatic islet beta-cells because of autoimmune damage. Patients with this type of diabetes need lifelong treatment with insulin to remain alive. Poor diabetic control which predisposes to a variety of complications is not uncommon in patients treated with insulin alone. Therefore, the use of medications that can possibly enhance the therapeutic effect of insulin and reduce the risk of diabetic complications has been considered.
Oral anti-diabetics including acarbose, an inhibitor of intestinal α-glucosidase, metformin, a biguanide, sulfonylureas including glipizide, and sitagliptin, an inhibitor of dipeptidyl peptidase 4 (DPP-4) are primarily used for the treatment of non-insulin dependent diabetes (Type 2).
The aim of this paper is to provide an overview of the use of oral anti-diabetics in the treatment of insulin dependent diabetes (Type 1).
Expert opinion: The current evidence-based expert opinion recommends the judicious use of oral anti-diabetics especially acarbose and metformin in the treatment of unsatisfactorily controlled insulin dependent diabetes type 1. These medications can help in improving diabetic control through reducing glucose levels after meals, and can contribute to lowering the levels of glycosylated hemoglobin (HbA1c). The use of these oral anti-diabetics can also help in reducing insulin requirement.
Acarbose is first of the inhibitors of intestinal alpha-glucosidase to be introduced as an oral anti-diabetic medication.
In 1983, McCulloch and colleagues reported a double-blind crossover study which included 14 patients with insulin-dependent diabetes who received acarbose, alpha-glucosidase inhibitor for six weeks with the aim preventing nocturnal hypoglycemia.
Six patients received acarbose 200 mg, and mid-evening hypoglycemia in association with severe abdominal colic and flatulence. Eight patients received acarbose 100 mg before the evening meal, and experienced considerable reduction in nocturnal hypoglycemic attacks and midevening hypoglycemia [1].
In 1991, Marena et al reported a placebo-controlled study which included fourteen patients with insulin-dependent diabetes type 1 (insulin-dependent) who had normal weight and poorly controlled hyperglycemia. The patients received either 100 mg acarbose or placebo three times daily for six weeks.
Thereafter, the usual insulin treatment was replaced with an artificial B-cell insulin delivery that was programmed for euglycemia. Acarbose or placebo was continued before meals.
The study showed that acarbose reduced mean blood glucose levels (P=0.002) and HbA1c levels (P below 0.001). Marena et al suggested that acarbose can contribute to a better control of hyperglycemia diabetes type 1 and also help in decreasing insulin requirement [2].
In 1993, Escobar-Jiménez et al reported a multi-center placebo-controlled study which included 137 patients with diabetes type 1 (Insulin-dependent). During the first part of the study (3 months), patients received either acarbose 50 mg three times daily or placebo for one month, and thereafter, they received either acarbose 100 mg three times daily or placebo for two months. After 1 month of wash out with placebo, the patients received the inverse medication for 3 more months (Second part of the study). The most important side effects were meteorism and flatulence. The use of acarbose was associated with reduction of glycemia after meals (P=0.007), and glycosylated hemoglobin HbA1 (P= 0.0005) [3].
In 1997, Hollander and colleagues reported a multi-center placebo-controlled study which included patients with diabetes type 1 (Insulin-dependent) who treated with either acarbose 50 to 300 mg 3 times daily or placebo for 36 weeks. The use of acarbose reduced mean glucose levels 60 minutes after a test meal 59 mg/dl, and also reduced mean HbA1c levels 0.48%. Acarbose was found to be safe, and the most important side effects included flatulence, abdominal pain, and diarrhea [4].
In 1998, Sels and colleagues reported a multi-center placebo-controlled study which included 62 adults (35 males and 27 females) with diabetes type 1, aged 18-64 years (Mean age: 38 years). Patients received either acarbose 75-300 mg (Mean: 200 mg daily) or placebo. Treatment with acarbose for 8 and 16 reduced glycosylated hemoglobin (HbA1c) levels (P < 0>
Sels and colleagues recommended using acarbose up 100 mg three times daily to improve the control diabetes type 1 [5].
In 1999, Riccardi et al from Italy reported a multi-center placebo-controlled study which included 121 patients with unsatisfactorily controlled diabetes mellitus type 1. Patients received acarbose or placebo plus diet high- or low in fiber for 24 weeks. Acarbose was given I am dose of 50 mg three times daily during the first 2 weeks, and 100 mg three times daily during the following weeks.
Compared with placebo, acarbose reduced plasma glucose levels measured two hours after meals (P < 0>
In 2000, Juntti-Berggren from Sweden reported a placebo-controlled study which showed that acarbose in a dose of 100 mg can considerably decrease mean insulin requirement in patients with diabetes type 1 over a three-hour period after meals without affecting gastric emptying [7].
In 2012, Yan-rong Ma and colleagues from China reported a study which showed that the addition of acarbose 50 mg to insulin in patients with diabetes type 1 can markedly lessen fluctuations in glucose level and reduce insulin dosage [8].
In 1985, Gin et al reported a placebo-controlled study which included 10 patients with diabetes mellitus type I diabetic who had normal weight. The patients received either metformin 850 mg two times a day or placebo for one week. Metformin improved insulin action by improving glucose uptake 18% (P less than 0.01). The beneficial effects of metformin were attributed to increasing insulin binding to insulin receptors [9].
In 1985, Leblanc et al from France reported a placebo-controlled study which included ten obese patients with poorly controlled insulin requiring diabetes in spite of treatment with large doses of lente insulin given once daily. The showed that the use of metformin 2550 mg daily improved insulin resistance and reduced insulin requirement [10].
In 2001, Lacigová et al reported a placebo-controlled study which included nineteen patients with poorly controlled diabetes type 1 who had insulin resistance. Three months treatment with metformin 850 mg twice daily resulted in an improvement in glycemic control in association with a decrease in insulin requirements (P < 0>
In 2002, Ricardo Gómez from the United States and his research group emphasized that metformin can decrease blood glucose by decreasing glucose output from the liver and improving resistance to insulin sensitivity without increasing insulin level.
They conducted a study which included ten adolescents and young adults (4 males, 6 females) with diabetes mellitus type 1. The patients were treated initially with metformin 250 mg twice daily, and the dose was increased to a maximum of 2500 mg daily to achieve an acceptable blood glucose level. Seven of the ten patients experienced a mean reduction in glycosylated hemoglobin (HbA1c) of 11% from before metformin treatment [12].
Also in 2002, Laurent Meyer and his research group from France reported a placebo-controlled study which included 62 patients (37 males and 25 females) who had diabetes mellitus type 1. Metformin treatment 850 mg twice daily was associated with a lower insulin requirement compared with an increased insulin requirements in patients who received placebo (P = 0.0043).
Metformin treatment was also associated with marked lowering of total cholesterol (P = 0.04) and LDL cholesterol (P = 0.05).
Three patients stopped metformin because of the occurrence of abdominal pain and diarrhea.
Milder gastrointestinal unwanted effects also occurred in eight patients who received metformin and two patients who received placebo (P = 0.069).
Laurent Meyer and his research group considered metformin to be safe, and has a beneficial insulin-sparing effect in diabetes type 1[13].
In 2003, Jill Hamilton from Canada and her research group reported a 3-month placebo-controlled study which included 27 adolescents with diabetes type 1 with high insulin daily requirement more than 1 unit/ kg (plus/minus 1), and high glycosylated hemoglobin (HbA1c >8%). Treatment with metformin decreased insulin requirement and also reduced HbA1c 0.6% more than in the placebo group (P < 0 xss=removed>
Also in 2003, Stefan Särnblad from Sweden and his colleagues reported a 3-month placebo-controlled study which included 26 adolescents with diabetes type 1 (8 males and 18 females) with high insulin daily requirement more than 1.2 unit/ kg (plus/minus 0.3), and high glycosylated hemoglobin levels (HbA1c about 9.5%). The patients received either metformin or placebo. Metformin treatment considerably reduced glycosylated hemoglobin from 9.6 to 8.7% (P<0>
In 2015, Cong Liu from China and his colleagues conducted a meta-analysis which included 8 published randomized controlled trials studies which showed that the use of metformin in diabetes type 1 decreased daily insulin requirement, and weight and improved lipids profile. The use of metformin did not increase risk of hypoglycemia and ketoacidosis. However, gastrointestinal symptoms occurred more with metformin than with placebo [16].
In 2011, Ellis et al from the United States reported a study which included 20 adults with diabetes type 1. Patients received sitagliptin 100 mg daily or placebo for 4 weeks, and then crossed over. The study showed that sitagliptin improved glycemic control. Compared with placebo, sitagliptin markedly lowered 2-hour postprandial blood glucose and 24-h glucose control despite reduction in total and prandial insulin dose.
The addition of sitagliptin markedly reduced insulin dose, and considerably lowered glycosylated hemoglobin (HbA1c) levels. The beneficial effects of sitagliptin were attributed to the lowering of the increased postprandial glucagon secretion by increasing glucose-dependent insulinotropic peptide and glucagon-like peptide 1 levels [17].
However, in 2013, Satish K Garg from the United States reported a placebo-controlled study which included 141 patients with diabetes type 1 who received either sitagliptin 100 mg daily or placebo for sixteen weeks. The study showed that sitagliptin had no significant beneficial effects on hyperglycemia, weight and insulin requirement [18].
In 1990, Leblanc et al reported a placebo-controlled study which included nine adults with diabetes mellitus type 1 (insulin dependent) who had normal BMI. Patients were randomized to receive either glipizide15 mg a day or placebo. The study showed that adding glipizide patients with diabetes mellitus type 1 to insulin treatment was not associated with improvement the glycemic control nor resulted in improvement insulin sensitivity [19].
In 1993, Selam et al a study which included 27 patients with recent development of diabetes type 1 who were treated with intensive subcutaneous injections for one month. The insulin was either discontinued or withdrawn and glipizide started. Three patients who had their insulin withdrawn (22%) experienced insulin-free remissions for 10.3 +/- 4.4 and 8.7 +/- 2.6 months, and seven patients who started glipizide (54%) experienced insulin-free remissions for 10.3 +/- 4.4 and 8.7 +/- 2.6 months.
The study suggested that treatment with insulin and glipizide was associated with more remissions than intensive treatment with insulin only. Selam et al thought that glipizide may have affected insulin sensitivity or possibly exerted an immunomodulatory effect [20].
The use of other oral anti-diabetic medications including sodium-glucose co-transporter (SGLT) inhibitors, liraglutide, glibenclamide, and empagliflozin in diabetes type 1 has also been reported [21].
The current evidence-based expert opinion recommends the judicious use of oral anti-diabetics especially acarbose and metformin in the treatment of unsatisfactorily controlled insulin dependent diabetes type 1. These medications can help in improving diabetic control through reducing glucose levels after meals, and can contribute to lowering the levels of glycosylated hemoglobin (HbA1c). The use of these oral anti-diabetics can also help in reducing insulin requirement.
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