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Therapeutic Medications Against Diabetes: What We Have and What We Expect

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Therapeutic Medications Against Diabetes: What We Have and What We Expect Advanced Drug Delivery Reviews 139 (2019) 3–15 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr Therapeutic medications against diabetes: What we have and what we expect Cheng Hu a,b, Weiping Jia a,⁎ a Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, People's Republic of China b Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, 6600 Nanfeng Road, Shanghai 200433, People's Republic of China article info abstract Article history: Diabetes has become one of the largest global health and economic burdens, with its increased prevalence and Received 28 June 2018 high complication ratio. Stable and satisfactory blood glucose control are vital to reduce diabetes-related compli- Received in revised form 1 September 2018 cations. Therefore, continuous attempts have been made in antidiabetic drugs, treatment routes, and traditional Accepted 27 November 2018 Chinese medicine to achieve better disease control. New antidiabetic drugs and appropriate combinations of Available online 5 December 2018 these drugs have increased diabetes control significantly. Besides, novel treatment routes including oral antidia- betic peptide delivery, nanocarrier delivery system, implantable drug delivery system are also pivotal for diabetes Keywords: fi Diabetes control, with its greater ef ciency, increased bioavailability, decreased toxicity and reduced dosing frequency. Treatment Among these new routes, nanotechnology, artificial pancreas and islet cell implantation have shown great poten- Drug delivery tial in diabetes therapy. Traditional Chinese medicine also offer new options for diabetes treatment. Our paper Natural product aim to overview these therapeutic methods for diabetes therapy. Proper combinations of these existing anti- diabetic medications and searching for novel routes are both necessary for better diabetes control. © 2018 Published by Elsevier B.V. Contents 1. Introduction............................................................... 4 2. Treatmentofdiabetes........................................................... 4 2.1. Metformin............................................................ 4 2.2. Sulfonylurea............................................................ 5 2.3. Glinides.............................................................. 5 2.4. Thiazolidinediones......................................................... 5 2.5. GLP-1RAsandDPP-4inhibitors................................................... 6 2.6. SGLT2inhibitors.......................................................... 6 2.7. Insulin.............................................................. 6 3. Promisingtherapeuticroutesforpatientswithdiabetes........................................... 6 3.1. Oralantidiabeticpeptidedelivery.................................................. 6 3.1.1. Overcomingdigestivedestruction.............................................. 7 3.1.2. Enhancingtheabsorptionandtransformationofpeptides................................... 8 3.2. Nanocarrierdeliverysystem..................................................... 8 3.2.1. Liposomes........................................................ 9 3.2.2. Niosomes......................................................... 9 3.2.3. Polymericnanoparticles.................................................. 9 3.2.4. Polyamidoaminedendrimers................................................ 9 3.2.5. Polymericmicelles..................................................... 9 3.3. Implantabledrugdeliverysystem.................................................. 9 3.3.1. Insulinpumptherapy................................................... 10 3.3.2. Artificialpancreas..................................................... 10 ⁎ Corresponding author. E-mail address: [email protected] (W. Jia). https://doi.org/10.1016/j.addr.2018.11.008 0169-409X/© 2018 Published by Elsevier B.V. 4 C. Hu, W. Jia / Advanced Drug Delivery Reviews 139 (2019) 3–15 3.4. Isletcelltransplantation.......................................................10 4. Naturalproducts.............................................................11 5. Summary.................................................................11 Dualityofinterest...............................................................12 Funding....................................................................12 Authorcontributions..............................................................12 References...................................................................12 1. Introduction force [16]. Importantly, diabetes accounts for approximately 10.7% of global all-cause mortality, which is higher than the rate associated Diabetes is a complex, chronic disease characterized by deficient with infectious diseases. Approximately 4.0 million deaths between β-cell insulin secretion in the setting of insulin resistance. Currently, di- the ages of 20 and 79 years were attributed to diabetes in 2017 [1]. abetes is one of the largest global health threats and is included among In addition to the human burden, diabetes also imposes serious eco- the top 3 noncommunicable diseases that account for over 80% of all nomic pressures on countries and their healthcare systems. IDF showed premature noncommunicable disease-related deaths; furthermore, it a significant growing healthcare expenditure from 232 billion USD in is among the top 10 causes of death worldwide. Its global prevalence 2007 to 727 billion USD in 2017 by 20- to 79-year-olds with diabetes. has rapidly increased over the past several decades. According to the This economic burden is estimated to increase to 776 billion USD by most recent edition of the International Diabetes Federation (IDF) Dia- 2045 [1]. Another global economic analysis using epidemiological and betes Atlas [1], 425 million 20- to 79-year-olds have diabetes (preva- demographic data from 180 countries in 2015 also indicated similar lence, 8.8%), and this value increases to 451 million when the age global trends, namely, the costs of diabetes are tremendous and will range is expanded to 18- to 99-year-olds. If this trend continues, the continue to increase through 2030 [17]. These economic effects will numbers of 20- to 79-year-olds and 18- to 99-year-olds with diabetes not be attenuated even if countries meet the “Sustainable Development will each increase to 629 million and 693 million, respectively, by Goal”. 2045. This large increase in diabetes is the result of population growth, aging, and the economic transition from low to middle income levels. 2. Treatment of diabetes Across IDF regions, the prevalence of diabetes differs by region and country. The age-adjusted comparative prevalence among 20- to 79- Antidiabetic drugs are a fundamental strategy for managing year-olds was highest in North America and the Caribbean (11.0%) T2DM. Current commonly used antidiabetic drugs include the following and lowest in Africa (4.2%) in 2017, most likely because of lower levels categories: metformin, sulfonylureas, glinides, thiazolidinediones, of urbanization and obesity as well as higher levels of under-nutrition in α-glucosidase inhibitors, incretin-based agent-like glucagon-like Africa. The 3 countries with the largest numbers of people with diabetes peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) in- in 2017 were China, India and the United States. Moreover, it is esti- hibitors, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and mated that approximately 50% (212.4 million) of adults with diabetes insulin. are undiagnosed, and 7.3% (352.1 million) of adults have impaired glu- Fig. 1 shows target organs and mechanism of different types of anti- cose tolerance. Therefore, it is imperative to screen the high-risk popu- diabetic drugs except insulin. lation and provide appropriate recommendations for people with diabetes. 2.1. Metformin The classification of diabetes is complex, but it is now widely ac- knowledged that there are three main types of diabetes, type 1 diabetes As the only type of biguanide approved for the clinical treatment of mellitus (T1DM), type 2 diabetes mellitus (T2DM) and gestational dia- diabetes [18], metformin remains the first-line treatment, especially betes mellitus (GDM). Besides, there are also some less common types for obese patients [19–21]. Metformin is not only used for the glycemic of diabetes which include monogenic diabetes and secondary diabetes. control of patients with T2DM but also to delay or prevent the progres- As the most common type of diabetes, T2DM accounts for around 90% of sion of impaired fasting glucose and impaired glucose tolerance into all cases of diabetes. Patients with T2DM have increased rates of macro- T2DM [22,23]. The hypoglycemic mechanism of metformin is still not and micro-vascular complications, which contribute to increased pre- fully understood [24–26]. Metformin is traditionally thought to increase mature mortality and lower quality of life for both these patients and liver insulin sensitivity by reducing hepatic glucose production. Metfor- their families. Moreover, the control of diabetes remains unsatisfactory. min inhibits mitochondrial Complex I, preventing ATP production, According to the United States National Health and Nutrition Examina- thereby increasing AMP/ATP and ADP/ATP ratios, thus activating AMP-
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