Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial: Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators; Received August 7, 2023 Accepted November 30, 2023 Published online April 23, 2024; DOI: https://doi.org/10.4093/dmj.2023.0259 [Epub ahead of print]

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Abstract PDF: Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Drug Regimen
Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension: Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon; Diabetes Metab J. 2023;47(6):808-817. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0387

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Drug Regimen
Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial: Kyung Ah Han, Yong Hyun Kim, Doo Man Kim, Byung Wan Lee, Suk Chon, Tae Seo Sohn, In Kyung Jeong, Eun-Gyoung Hong, Jang Won Son, Jae Jin Nah, Hwa Rang Song, Seong In Cho, Seung-Ah Cho, Kun Ho Yoon; Diabetes Metab J. 2023;47(6):796-807. Published online February 9, 2023; DOI: https://doi.org/10.4093/dmj.2022.0315

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Background
Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500).
Results
Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated.
Conclusion
Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Citations

Citations to this article as recorded by

Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials
Young Sang Lyu, Sangmo Hong, Si Eun Lee, Bo Young Cho, Cheol-Young Park
Cardiovascular Diabetology.2024;[Epub] CrossRef
A 52‐week efficacy and safety study of enavogliflozin versus dapagliflozin as an add‐on to metformin in patients with type 2 diabetes mellitus: ENHANCE‐M extension study
Tae Seo Sohn, Kyung‐Ah Han, Yonghyun Kim, Byung‐Wan Lee, Suk Chon, In‐Kyung Jeong, Eun‐Gyoung Hong, Jang Won Son, JaeJin Na, Jae Min Cho, Seong In Cho, Wan Huh, Kun‐Ho Yoon
Diabetes, Obesity and Metabolism.2024;[Epub] CrossRef
The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium‐glucose cotransporter‐2 inhibitor, in type 2 diabetes
Sae Im Jeong, Mu Seong Ban, Jun‐Gi Hwang, Min‐Kyu Park, Soo Lim, Sejoong Kim, Soon Kil Kwon, Yoonjin Kim, Jae Min Cho, Jae Jin Na, Wan Huh, Jae‐Yong Chung
Diabetes, Obesity and Metabolism.2024;[Epub] CrossRef
Role of novel sodium glucose co-transporter-2 inhibitor enavogliflozin in type-2 diabetes: A systematic review and meta-analysis
Deep Dutta, B.G. Harish, Beatrice Anne, Lakshmi Nagendra
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(8): 102816. CrossRef
Characteristics of the Latest Therapeutic Agent for Diabetes
Nuri Yun
The Journal of Korean Diabetes.2023; 24(3): 148. CrossRef
Prospects of using sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with metabolic-associated fatty liver disease (MAFLD)
Iryna Kostitska, Nadia Protas, Liliia Petrovska
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Brief Report

Drug/Regimen
Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Soon-Jib Yoo, Sang-Ah Chang, Tae Seo Sohn, Hyuk-Sang Kwon, Jong Min Lee, Sungdae Moon, Pieter Proot, Päivi M Paldánius, Kun Ho Yoon; Diabetes Metab J. 2021;45(6):954-959. Published online November 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0173

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We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

Citations

Citations to this article as recorded by

2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
Diabetes & Metabolism Journal.2023; 47(5): 575. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef

Review

Drug/Regimen
Evaluating the Evidence behind the Novel Strategy of Early Combination from Vision to Implementation: Päivi Maria Paldánius; Diabetes Metab J. 2020;44(6):785-801. Published online September 15, 2020; DOI: https://doi.org/10.4093/dmj.2020.0179

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Abstract PDF PubReader ePub: Type 2 diabetes mellitus (T2DM) is a complex and progressive chronic disease characterised by elevating hyperglycaemia and associated need to gradually intensify therapy in order to achieve and maintain glycaemic control. Treating hyperglycaemia with sequential therapy is proposed to allow holistic assessment of the efficacy and risk-to-benefit ratio of each added component. However, there is an array of evidence supporting the scientific rationale for using synergistic, earlier, modern drug combinations to achieve glycaemic goals, delay the deterioration of glycaemic control, and, therefore, potentially preserve or slow down the declining β-cell function. Additionally, implementation of early combination(s) may lead to opportunities to combat clinical inertia and other hurdles to optimised disease management outcomes. This review aims to discuss the latest empirical evidence for long-term clinical benefits of this novel strategy of early combination in people with newly diagnosed T2DM versus the current widely-implemented treatment paradigm, which focuses on control of hyperglycaemia using lifestyle interventions followed by sequentially intensified (mostly metformin-based) monotherapy. The recent reported Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM (VERIFY) study results have provided significant new evidence confirming long-term glycaemic durability and tolerability of a specific early combination in the management of newly diagnosed, treatment-naïve patients worldwide. These results have also contributed to changes in clinical treatment guidelines and standards of care while clinical implementation and individualised treatment decisions based on VERIFY results might face barriers beyond the existing scientific evidence.

Original Article

Drug/Regimen
Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats: Sun Hee Kim, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2020;44(6):842-853. Published online May 28, 2020; DOI: https://doi.org/10.4093/dmj.2019.0190

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Background

Metformin is widely marketed medication for the treatment of diabetes, but its pharmacological effect on diabetic peripheral neuropathy remains unclear. In this study, the effect of metformin on peripheral nerves in diabetic rats was investigated using diverse neuronal parameters of nerve fibers.

Methods

Rats were assigned to one of four groups (n=7 to 10 per group): normal, diabetes mellitus (DM), DM+metformin (100 mg/kg), and DM+alpha lipoic acid (ALA, 100 mg/kg). DM was induced by streptozotocin/high-fat diet (STZ/HFD). After 12 weeks, the sensory thresholds to mechanical and heat stimuli were assessed. Repeated sensory tests, immunofluorescence microscopic comparison of peripheral nerves, and biochemical blood analysis were performed after 24 weeks.

Results

Both DM+metformin and DM+ALA groups showed similar trends to diverse sensory tests at 24 weeks compared to DM group although the degree of change were different according to the stimulated senses. There was no significant difference in the comparison of the intraepidermal nerve fiber density (IENFD) of peripheral nerves between the DM+metformin and DM+ALA groups (11.83±0.07 fibers/mm vs. 12.37±1.82 fibers/mm, respectively). Both groups showed preserved IENFD significantly compared with DM group (8.46±1.98 fibers/mm, P<0.05). Sciatic nerve morphology of the experimental animals showed a similar trend to the IENFD, with respect to axonal diameter, myelin sheath thickness, and myelinated fiber diameter.

Conclusion

Metformin has beneficial pharmacological effects on the preservation of peripheral nerves in diabetic rats and its effects are comparable to those of ALA.

Citations

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Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress
Fengmin Liu, Fangqin You, Lihang Yang, Siyun Wang, Diya Xie
Journal of Diabetes and its Complications.2024; : 108737. CrossRef
Effect of Metformin on the Functional and Electrophysiological Recovery of Crush Injury-Induced Facial Nerve Paralysis in Diabetic Rats
Kyung Hoon Sun, Cheol Hee Choi, Gwang-Won Cho, Chul Ho Jang
Journal of Personalized Medicine.2023; 13(9): 1317. CrossRef
Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis
Fatemeh Karami, Hamidreza Jamaati, Natalie Coleman-Fuller, Maryam Shokrian Zeini, A. Wallace Hayes, Mina Gholami, Mahsa Salehirad, Mohammad Darabi, Majid Motaghinejad
Pharmacological Reports.2023; 75(3): 511. CrossRef
Early Diagnosis through Estimation of Inflammatory Biomarkers and the Neuroprotective Role of Metformin in Diabetic Peripheral Neuropathy
Laxmi Sri, Prabhakar Orsu
International Journal of Pharmaceutical Sciences and Nanotechnology(IJPSN).2023; 16(2): 6427. CrossRef
Bidirectional association between diabetic peripheral neuropathy and vitamin B12 deficiency: Two longitudinal 9-year follow-up studies using a national sample cohort
Heung Yong Jin, Kyung Ae Lee, Yu Ji Kim, In Sun Gwak, Tae Sun Park, Sang Woo Yeom, Jong Seung Kim
Primary Care Diabetes.2023; 17(5): 436. CrossRef
An overview of painful diabetic peripheral neuropathy: Diagnosis and treatment advancements
Jonathan M. Hagedorn, Alyson M. Engle, Tony K. George, Jay Karri, Newaj Abdullah, Erik Ovrom, Jhon E. Bocanegra-Becerra, Ryan S. D'Souza
Diabetes Research and Clinical Practice.2022; 188: 109928. CrossRef
The role of MicroRNA networks in tissue-specific direct and indirect effects of metformin and its application
Qinzhi Yang, Gang Wang, Dan Fang, Xiaojun Gao, Yu Liang, Liqun Wang, Jianbo Wu, Min Zeng, Mao Luo
Biomedicine & Pharmacotherapy.2022; 151: 113130. CrossRef
Is metformin a possible treatment for diabetic neuropathy?
Juechun Wei, Yanling Wei, Meiyan Huang, Peng Wang, Shushan Jia
Journal of Diabetes.2022; 14(10): 658. CrossRef
Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system
Sarah Demaré, Asha Kothari, Nigel A. Calcutt, Paul Fernyhough
Expert Review of Neurotherapeutics.2021; 21(1): 45. CrossRef
Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats (Diabetes Metab J 2020;44:842-53)
Bo Kyung Koo
Diabetes & Metabolism Journal.2021; 45(1): 125. CrossRef
Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats (Diabetes Metab J 2020;44:842-53)
Sun Hee Kim, Tae Sun Park, Heung Yong Jin
Diabetes & Metabolism Journal.2021; 45(1): 127. CrossRef
Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data
Hong Ki Min, Se Hee Kim, Jong Han Choi, Kyomin Choi, Hae-Rim Kim, Sang-Heon Lee
World Journal of Clinical Cases.2021; 9(33): 10198. CrossRef

Review

Guideline/Fact Sheet
Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement: Kyu Yeon Hur, Mee Kyoung Kim, Seung Hyun Ko, Miyeun Han, Dong Won Lee, Hyuk-Sang Kwon; Diabetes Metab J. 2020;44(1):3-10. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0004

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The safety of metformin use for patients with type 2 diabetes mellitus (T2DM) and advanced kidney disease is controversial, and more recent guidelines have suggested that metformin be used cautiously in this group until more definitive evidence concerning its safety is available. The Korean Diabetes Association and the Korean Society of Nephrology have agreed on consensus statements concerning metformin use for patients with T2DM and renal dysfunction, particularly when these patients undergo imaging studies using iodinated contrast media (ICM). Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is ≥45 mL/min/1.73 m². If the eGFR is between 30 and 44 mL/min/1.73 m², metformin treatment should not be started. If metformin is already in use, a daily dose of ≤1,000 mg is recommended. Metformin is contraindicated when the eGFR is <30 mL/min/1.73 m². Renal function should be evaluated prior to any ICM-related procedures. During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours post-procedures if the eGFR is <60 mL/min/1.73 m².

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Prediction of glycosylated hemoglobin level in patients with cardiovascular diseases and type 2 diabetes mellitus with respect to anti-diabetic medication
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Frontiers in Endocrinology.2024;[Epub] CrossRef
Determinants of vitamin B12 deficiency in patients with type-2 diabetes mellitus — A primary-care retrospective cohort study
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Risk factors for post-contrast acute kidney injury in patients sequentially administered iodine- and gadolinium-based contrast media on the same visit to the emergency department: a retrospective study
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Iranian Journal of Blood and Cancer.2023; 15(4): 293. CrossRef
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European Radiology.2022; 32(5): 3045. CrossRef
Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Cardiovascular Disease: The Past, Present, and Future
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American Journal of Cardiovascular Drugs.2022; 22(4): 363. CrossRef
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Treatment Patterns of Type 2 Diabetes Assessed Using a Common Data Model Based on Electronic Health Records of 2000–2019
Kyung Ae Lee, Heung Yong Jin, Yu Ji Kim, Yong-Jin Im, Eun-Young Kim, Tae Sun Park
Journal of Korean Medical Science.2021;[Epub] CrossRef
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
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Diabetes & Metabolism Journal.2021; 45(6): 972. CrossRef
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Original Articles

Pathophysiology
Metformin Ameliorates Lipotoxic β-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action: Hong Il Kim, Ji Seon Lee, Byung Kook Kwak, Won Min Hwang, Min Joo Kim, Young-Bum Kim, Sung Soo Chung, Kyong Soo Park; Diabetes Metab J. 2019;43(6):854-866. Published online June 27, 2019; DOI: https://doi.org/10.4093/dmj.2018.0179

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Background

Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.

Methods

NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.

Results

We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.

Conclusion

This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.

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Heliyon.2024; 10(2): e24432. CrossRef
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Sevda Gheibi, Luis Rodrigo Cataldo, Alexander Hamilton, Mi Huang, Sebastian Kalamajski, Malin Fex, Hindrik Mulder
Diabetes.2023; 72(4): 455. CrossRef
Metformin restores prohormone processing enzymes and normalizes aberrations in secretion of proinsulin and insulin in palmitate‐exposed human islets
Quan Wen, Azazul Islam Chowdhury, Banu Aydin, Mudhir Shekha, Rasmus Stenlid, Anders Forslund, Peter Bergsten
Diabetes, Obesity and Metabolism.2023; 25(12): 3757. CrossRef
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Priyamvada Amol Arte, Kanchanlata Tungare, Mustansir Bhori, Renitta Jobby, Jyotirmoi Aich
Human Cell.2023; 37(1): 54. CrossRef
Metformin disrupts insulin secretion, causes proapoptotic and oxidative effects in rat pancreatic beta‐cells in vitro
Maíra M.R. Valle, Eloisa Aparecida Vilas‐Boas, Camila F. Lucena, Simone A. Teixeira, Marcelo N. Muscara, Angelo R. Carpinelli
Journal of Biochemical and Molecular Toxicology.2022;[Epub] CrossRef
Protection by metformin against severe Covid-19: An in-depth mechanistic analysis
Nicolas Wiernsperger, Abdallah Al-Salameh, Bertrand Cariou, Jean-Daniel Lalau
Diabetes & Metabolism.2022; 48(4): 101359. CrossRef
Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis
Lei Wei, Jianjian Shi
Frontiers in Endocrinology.2022;[Epub] CrossRef
Overexpression of miR-297b-5p Promotes Metformin-Mediated Protection Against Stearic Acid-Induced Senescence by Targeting Igf1r
Qingrui Zhao, Shenghan Su, Yuqing Lin, Xuebei Li, Lingfeng Dan, Yunjin Zhang, Chunxiao Yang, Xiaohan Li, Yimeng Dong, Chenchen Geng, Changhao Sun, Xia Chu, Huimin Lu
SSRN Electronic Journal .2022;[Epub] CrossRef
Metformin Dysregulates the Unfolded Protein Response and the WNT/β-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism
Domenico Conza, Paola Mirra, Gaetano Calì, Luigi Insabato, Francesca Fiory, Francesco Beguinot, Luca Ulianich
Cells.2021; 10(5): 1067. CrossRef
NADPH Oxidase (NOX) Targeting in Diabetes: A Special Emphasis on Pancreatic β-Cell Dysfunction
Suma Elumalai, Udayakumar Karunakaran, Jun-Sung Moon, Kyu-Chang Won
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Metformin use and cardiovascular outcomes in patients with diabetes and chronic kidney disease: a nationwide cohort study
Min Ho Kim, Hyung Jung Oh, Soon Hyo Kwon, Jin Seok Jeon, Hyunjin Noh, Dong Cheol Han, Hyoungnae Kim, Dong-Ryeol Ryu
Kidney Research and Clinical Practice.2021; 40(4): 660. CrossRef
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Chi-Ming Chan, Ponarulselvam Sekar, Duen-Yi Huang, Shu-Hao Hsu, Wan-Wan Lin
Antioxidants.2020; 9(11): 1057. CrossRef
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Ximei Shen, Beibei Fan, Xin Hu, Liufen Luo, Yuanli Yan, Liyong Yang
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Clinical Diabetes & Therapeutics
Additional Effect of Dietary Fiber in Patients with Type 2 Diabetes Mellitus Using Metformin and Sulfonylurea: An Open-Label, Pilot Trial: Seung-Eun Lee, Yongbin Choi, Ji Eun Jun, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Gwang Pyo Ko, Moon-Kyu Lee; Diabetes Metab J. 2019;43(4):422-431. Published online April 23, 2019; DOI: https://doi.org/10.4093/dmj.2018.0090

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Background

Metformin, sulfonylurea, and dietary fiber are known to affect gut microbiota in patients with type 2 diabetes mellitus (T2DM). This open and single-arm pilot trial investigated the effects of the additional use of fiber on glycemic parameters, insulin, incretins, and microbiota in patients with T2DM who had been treated with metformin and sulfonylurea.

Methods

Participants took fiber for 4 weeks and stopped for the next 4 weeks. Glycemic parameters, insulin, incretins during mixed-meal tolerance test (MMTT), lipopolysaccharide (LPS) level, and fecal microbiota were analyzed at weeks 0, 4, and 8. The first tertile of difference in glucose area under the curve during MMTT between weeks 0 and 4 was defined as ‘responders’ and the third as ‘nonresponders,’ respectively.

Results

In all 10 participants, the peak incretin levels during MMTT were higher and LPS were lower at week 4 as compared with at baseline. While the insulin sensitivity of the ‘responders’ increased at week 4, that of the ‘nonresponders’ showed opposite results. However, the results were not statistically significant. In all participants, metabolically unfavorable microbiota decreased at week 4 and were restored at week 8. At baseline, metabolically hostile bacteria were more abundant in the ‘nonresponders.’ In ‘responders,’ Roseburia intestinalis increased at week 4.

Conclusion

While dietary fiber did not induce additional changes in glycemic parameters, it showed a trend of improvement in insulin sensitivity in ‘responders.’ Even if patients are already receiving diabetes treatment, the additional administration of fiber can lead to additional benefits in the treatment of diabetes.

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Sydney A. Dixon, Sidharth Mishra, Katrina B. Dietsche, Shalini Jain, Lilian Mabundo, Michael Stagliano, Andrea Krenek, Amber Courville, Shanna Yang, Sara A. Turner, Abby G. Meyers, Doris E. Estrada, Hariom Yadav, Stephanie T. Chung
Frontiers in Endocrinology.2023;[Epub] CrossRef
The impact of dietary, surgical, and pharmacological interventions on gut microbiota in individuals with diabetes mellitus: A systematic review
Patricia M. Bock, Andreza F. Martins, Rafaela Ramalho, Gabriela H. Telo, Gabriel Leivas, Clara K. Maraschin, Beatriz D. Schaan
Diabetes Research and Clinical Practice.2022; 189: 109944. CrossRef
Assessment of the safety and probiotic properties of Roseburia intestinalis: A potential “Next Generation Probiotic”
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Short Communication

Clinical Diabetes & Therapeutics
Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus: Sung Hye Kong, Bo Kyung Koo, Min Kyong Moon; Diabetes Metab J. 2019;43(5):711-717. Published online March 20, 2019; DOI: https://doi.org/10.4093/dmj.2018.0208

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Background

The study aimed to evaluate the effects of dapagliflozin and metformin on vascular endothelial function and renal injury markers.

Methods

This prospective, randomized, open-label, crossover study included drug-naïve patients with type 2 diabetes mellitus, who were randomized to receive 8 weeks of initial treatment using metformin or dapagliflozin and crossed over for another 8 weeks of treatment after a 1-week washout period. Systemic endothelial function was evaluated via the reactive hyperemic index (RHI).

Results

The 22 participants included 10 males (45.5%) and had a median age of 58 years. The RHI values were not significantly changed during both 8-week treatment periods and there was no significant difference between the treatments. Relative to the metformin group, 8 weeks of dapagliflozin treatment produced significantly higher median N-acetyl-beta-D-glucosaminidase levels (10.0 ng/mL [interquartile range (IQR), 6.8 to 12.1 ng/mL] vs. 5.6 ng/mL [IQR, 3.8 to 8.0 ng/mL], P=0.013). Only the dapagliflozin group exhibited improved homeostatic model assessment of insulin resistance and body weight, while serum ketone and β-hydroxybutyrate levels increased.

Conclusion

Dapagliflozin treatment did not affect systemic endothelial function or renal injury markers except N-acetyl-beta-D-glucosaminidase.

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Pharmacological Research.2023; 188: 106659. CrossRef
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Rujia Miao, Renhe Yu, Hui Zhou, Lei Liu, Ting Peng, Jiangang Wang
BMJ Open.2023; 13(9): e073357. CrossRef
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Mariarosaria De Luca, Giulia Crisci, Giuseppe Armentaro, Sebastiano Cicco, Giovanni Talerico, Emanuele Bobbio, Lorena Lanzafame, Christopher G. Green, Abbie G. McLellan, Radek Debiec, Paolo Caferra, Roberto Scicali, Antonio Cannatà, Muhammad Zubair Israr,
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Vaneza Lira W. Wolf, Ikaro Breder, Luiz Sérgio F. de Carvalho, Alexandre A. S. Soares, Riobaldo M. Cintra, Joaquim Barreto, Daniel B. Munhoz, Sheila T. Kimura-Medorima, Wilson Nadruz, Gil Guerra-Júnior, Thiago Quinaglia, Elza Muscelli, Andrei C. Sposito
Nutrition & Diabetes.2021;[Epub] CrossRef
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Gloria M. Gager, Dirk von Lewinski, Harald Sourij, Bernd Jilma, Ceren Eyileten, Krzysztof Filipiak, Martin Hülsmann, Jacek Kubica, Marek Postula, Jolanta M. Siller-Matula
Biomedicine & Pharmacotherapy.2021; 143: 112169. CrossRef
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Marie-Sophie L.Y. de Koning, B. Daan Westenbrink, Solmaz Assa, Erwin Garcia, Margery A. Connelly, Dirk J. van Veldhuisen, Robin P.F. Dullaart, Erik Lipsic, Pim van der Harst
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Letter: Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019:43:711–7)
Dimitrios Patoulias, Michael Doumas
Diabetes & Metabolism Journal.2019; 43(6): 906. CrossRef
Response: Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019:43:711–7)
Sung Hye Kong, Bo Kyung Koo, Min Kyong Moon
Diabetes & Metabolism Journal.2019; 43(6): 913. CrossRef

Original Articles

Clinical Diabetes & Therapeutics
Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study: Hae Kyung Yang, Seung-Hwan Lee, Juyoung Shin, Yoon-Hee Choi, Yu-Bae Ahn, Byung-Wan Lee, Eun Jung Rhee, Kyung Wan Min, Kun-Ho Yoon; Diabetes Metab J. 2019;43(3):287-301. Published online December 20, 2018; DOI: https://doi.org/10.4093/dmj.2018.0054

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Background

We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.

Methods

A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.

Results

The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups.

Conclusion

In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

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Clinical Diabetes & Therapeutics
Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial: Tae Jung Oh, Jae Myung Yu, Kyung Wan Min, Hyun Shik Son, Moon Kyu Lee, Kun Ho Yoon, Young Duk Song, Joong Yeol Park, In Kyung Jeong, Bong Soo Cha, Yong Seong Kim, Sei Hyun Baik, In Joo Kim, Doo Man Kim, Sung Rae Kim, Kwan Woo Lee, Jeong Hyung Park, In Kyu Lee, Tae Sun Park, Sung Hee Choi, Sung Woo Park; Diabetes Metab J. 2019;43(3):276-286. Published online December 7, 2018; DOI: https://doi.org/10.4093/dmj.2018.0051

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Background

Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus.

Methods

A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24.

Results

The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039).

Conclusion

Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.

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Ashok Kumar, ShubhaLaxmi Margekar, Ravi Kumar
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Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Ki
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Sanjay Kalra, Ganapathi Bantwal, Nitin Kapoor, Rakesh Sahay, Saptarshi Bhattacharya, Beatrice Anne, Raju A Gopal, Sunil Kota, Ashok Kumar, Ameya Joshi, Debmalya Sanyal, Mangesh Tiwaskar, Ashok Kumar Das
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Pharmacological Research.2020; 159: 104988. CrossRef
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Diabetes & Metabolism Journal.2019; 43(4): 547. CrossRef
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Clinical Diabetes and Therapeutics
Hospital-Based Korean Diabetes Prevention Study: A Prospective, Multi-Center, Randomized, Open-Label Controlled Study: Sang Youl Rhee, Suk Chon, Kyu Jeung Ahn, Jeong-Taek Woo; Diabetes Metab J. 2019;43(1):49-58. Published online November 2, 2018; DOI: https://doi.org/10.4093/dmj.2018.0033

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Background

The prevalence of diabetes mellitus (DM) continues to increase, and the disease burden is the highest of any medical condition in Korea. However, large-scale clinical studies have not yet conducted to establish the basis for diabetes prevention in Korea.

Methods

The hospital-based Korean Diabetes Prevention Study (H-KDPS) is a prospective, multi-center, randomized, open-label controlled study conducted at university hospitals for the purpose of gathering data to help in efforts to prevent type 2 DM. Ten university hospitals are participating, and 744 subjects will be recruited. The subjects are randomly assigned to the standard care group, lifestyle modification group, or metformin group, and their clinical course will be observed for 36 months.

Results

All intervention methodologies were developed, validated, and approved by Korean Diabetes Association (KDA) multi-disciplinary team members. The standard control group will engage in individual education based on the current KDA guidelines, and the lifestyle modification group will participate in a professionally guided healthcare intervention aiming for ≥5% weight loss. The metformin group will begin dosing at 250 mg/day, increasing to a maximum of 1,000 mg/day. The primary endpoint of this study is the cumulative incidence of DM during the 3 years after randomization.

Conclusion

The H-KDPS study is the first large-scale clinical study to establish evidence-based interventions for the prevention of type 2 DM in Koreans. The evidence gathered by this study will be useful for enhancing the health of Koreans and improving the stability of the Korean healthcare system (Trial registration: CRIS KCT0002260, NCT02981121).

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Short Communication

Others
Synthesis of a New Zinc-Mixed Ligand Complex and Evaluation of Its Antidiabetic Properties in High Fat Diet: Low Dose Streptozotocin Induced Diabetic Rats: Muruganantham Koothappan, Roshana Devi Vellai, Iyyam Pillai Subramanian, Sorimuthu Pillai Subramanian; Diabetes Metab J. 2018;42(3):244-248. Published online April 24, 2018; DOI: https://doi.org/10.4093/dmj.2018.0002

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Abstract PDF PubReader

Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.

Citations

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A H Ismail, Z S Al-Garawi, K Al-Shamari, A T Salman
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A comprehensive review on zinc(II) complexes as anti-diabetic agents: The advances, scientific gaps and prospects
Chika Ifeanyi Chukwuma, Samson S. Mashele, Kenneth C. Eze, Godfrey R. Matowane, Shahidul Md. Islam, Susanna L. Bonnet, Anwar E.M. Noreljaleel, Limpho M. Ramorobi
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Review

Clinical Diabetes & Therapeutics
Monotherapy in Patients with Type 2 Diabetes Mellitus: Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim; Diabetes Metab J. 2017;41(5):349-356. Published online October 19, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.5.349

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70 Download
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Abstract PDF PubReader

In order to improve the quality of life and to prevent chronic complications related to diabetes mellitus, intensive lifestyle modification and proper medication are needed from the early stage of diagnosis of type 2 diabetes mellitus (T2DM). When using the first medication for diabetic patients, the appropriate treatment should be selected considering the clinical characteristics of the patient, efficacy of the drug, side effects, and cost. In general, the use of metformin as the first treatment for oral hypoglycemic monotherapy is recommended because of its excellent blood glucose-lowering effect, relatively low side effects, long-term proven safety, low risk of hypoglycemia, and low weight gain. If metformin is difficult to use as a first-line treatment, other appropriate medications should be selected in view of the clinical situation. If the goal of achieving glycemic control is not achieved by monotherapy, a combination therapy with different mechanisms of action should be initiated promptly.

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International Journal of Molecular Sciences.2019; 20(20): 5205. CrossRef
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