Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
Effects of Teneligliptin on HbA1c levels, Continuous Glucose Monitoring-Derived Time in Range and Glycemic Variability in Elderly Patients with T2DM (TEDDY Study): Ji Cheol Bae, Soo Heon Kwak, Hyun Jin Kim, Sang-Yong Kim, You-Cheol Hwang, Sunghwan Suh, Bok Jin Hyun, Ji Eun Cha, Jong Chul Won, Jae Hyeon Kim; Diabetes Metab J. 2022;46(1):81-92. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2021.0016

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Background
To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.
Methods
This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.
Results
After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).
Conclusion
Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

Citations

Citations to this article as recorded by

Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study
Harmanjit Singh, Ravi Rohilla, Shivani Jaswal, Mandeep Singla
Expert Review of Endocrinology & Metabolism.2024; 19(1): 81. CrossRef
Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects
Harmanjit Singh, Jasbir Singh, Ravneet Kaur Bhangu, Mandeep Singla, Jagjit Singh, Farideh Javid
Expert Review of Clinical Pharmacology.2023; 16(1): 49. CrossRef
Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights
Michelangelo Bauwelz Gonzatti, José Edvar Monteiro Júnior, Antônio José Rocha, Jonathas Sales de Oliveira, Antônio José de Jesus Evangelista, Fátima Morgana Pio Fonseca, Vânia Marilande Ceccatto, Ariclécio Cunha de Oliveira, José Ednésio da Cruz Freire
Advances in Medical Sciences.2023; 68(2): 402. CrossRef
A prospective multicentre open label study to assess effect of Teneligliptin on glycemic control through parameters of time in range (TIR) Metric using continuous glucose monitoring (TOP-TIR study)
Banshi Saboo, Suhas Erande, A.G. Unnikrishnan
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2022; 16(2): 102394. CrossRef
Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
Min Jeong Park, Kyung Mook Choi
Diabetes & Metabolism Journal.2022; 46(1): 49. CrossRef

COVID-19
Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19: Sang Youl Rhee, Jeongwoo Lee, Hyewon Nam, Dae-Sung Kyoung, Dong Wook Shin, Dae Jung Kim; Diabetes Metab J. 2021;45(2):251-259. Published online March 5, 2021; DOI: https://doi.org/10.4093/dmj.2020.0206

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Background
Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM).
Methods
As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset.
Results
Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682).
Conclusion
This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.

Citations

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Complication
Soluble Dipeptidyl Peptidase-4 Levels Are Associated with Decreased Renal Function in Patients with Type 2 Diabetes Mellitus: Eun-Hee Cho, Sang-Wook Kim; Diabetes Metab J. 2019;43(1):97-104. Published online October 8, 2018; DOI: https://doi.org/10.4093/dmj.2018.0030

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Background

Dipeptidyl peptidase-4 (DPP-4) is strongly expressed in the kidney, and soluble levels of this protein are used as a marker in various chronic inflammatory diseases, including diabetes, coronary artery disease, and cancer. This study examined the association between the serum soluble DPP-4 levels and renal function or cardiovascular risk in patients with type 2 diabetes mellitus.

Methods

In this retrospective analysis, soluble DPP-4 levels were measured in preserved sera from 140 patients with type 2 diabetes mellitus who had participated in our previous coronary artery calcium (CAC) score study.

Results

The mean±standard deviation soluble DPP-4 levels in our study sample were 645±152 ng/mL. Univariate analyses revealed significant correlations of soluble DPP-4 levels with the total cholesterol (r=0.214, P=0.019) and serum creatinine levels (r=−0.315, P<0.001) and the estimated glomerular filtration rate (eGFR; estimated using the modification of diet in renal disease equation) (r=0.303, P=0.001). The associations of soluble DPP-4 levels with serum creatinine and GFR remained significant after adjusting for age, body mass index, and duration of diabetes. However, no associations were observed between soluble DPP-4 levels and the body mass index, waist circumference, or CAC score.

Conclusion

These data suggest the potential use of serum soluble DPP-4 levels as a future biomarker of deteriorated renal function in patients with type 2 diabetes mellitus.

Citations

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Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway
Sarah M. AL-Qabbaa, Samaher I. Qaboli, Tahani K. Alshammari, Maha A. Alamin, Haya M. Alrajeh, Lama A. Almuthnabi, Rana R. Alotaibi, Asma S. Alonazi, Anfal F. Bin Dayel, Nawal M. Alrasheed, Nouf M. Alrasheed
International Journal of Molecular Sciences.2023; 24(7): 6532. CrossRef
Evaluation of the efficacy of dipeptidyl peptidase-4 enzyme and selenium element in people with kidney failure in Kirkuk governorate
Ibrahim Abdullah Ali Al-Jubouri, Nadia Ahmed Saleh Al-Jubouri
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Cardiovascular Effects of Incretin-Based Therapies: Integrating Mechanisms With Cardiovascular Outcome Trials
John R. Ussher, Amanda A. Greenwell, My-Anh Nguyen, Erin E. Mulvihill
Diabetes.2022; 71(2): 173. CrossRef
Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches
Harshit Sajal, Shashank M. Patil, Ranjith Raj, Abdullah M. Shbeer, Mohammed Ageel, Ramith Ramu
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Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes
Yewon Na, Soo Wan Kim, Ie Byung Park, Soo Jung Choi, Seungyoon Nam, Jaehun Jung, Dae Ho Lee
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Daiji Kawanami, Yuichi Takashi, Hiroyuki Takahashi, Ryoko Motonaga, Makito Tanabe
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Others
Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin: Jong Ho Kim, Sang Soo Kim, Hong Sun Baek, In Kyu Lee, Dong Jin Chung, Ho Sang Sohn, Hak Yeon Bae, Mi Kyung Kim, Jeong Hyun Park, Young Sik Choi, Young Il Kim, Jong Ryeal Hahm, Chang Won Lee, Sung Rae Jo, Mi Kyung Park, Kwang Jae Lee, In Joo Kim; Diabetes Metab J. 2016;40(3):230-239. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.230

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Background

We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.

Methods

The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.

Results

The mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002).

Conclusion

As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

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Review

Clinical Care/Education
Dipeptidyl Peptidase 4 Inhibitors and the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: A Tale of Three Studies: Jang Won Son, Sungrae Kim; Diabetes Metab J. 2015;39(5):373-383. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.373

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Dipeptidyl peptidase 4 (DPP4) inhibitors have been touted as promising antihyperglycemic agents due to their beneficial effects on glycemia without inducing hypoglycemia or body weight gain and their good tolerability. Beyond their glucose-lowering effects, numerous clinical trials and experimental studies have suggested that DPP4 inhibitors may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms or involving other substrates. Since 2008, regulatory agencies have required an assessment of cardiovascular disease (CVD) safety for the approval of all new anti-hyperglycemic agents, including incretin-based therapies. Three large prospective DPP4 inhibitor trials with cardiovascular (CV) outcomes have recently been published. According to the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) and EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE) trials, DPP4 inhibitors, including saxagliptin and alogliptin, did not appear to increase the risk of CV events in patients with type 2 diabetes and established CVD or high risk factors. Unexpectedly, saxagliptin significantly increased the risk of hospitalization for heart failure by 27%, a finding that has not been explained and that requires further exploration. More recently, the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) trial demonstrated the CV safety of sitagliptin, including assessments of the primary composite CV endpoint and hospitalization for heart failure in patients with type 2 diabetes and established CVD. The CV outcomes of an ongoing linagliptin trial are expected to provide new evidence about the CV effects of a DPP4-inhibitor in patients with type 2 diabetes.

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Original Article

Predictive Clinical Parameters and Glycemic Efficacy of Vildagliptin Treatment in Korean Subjects with Type 2 Diabetes: Jin-Sun Chang, Juyoung Shin, Hun-Sung Kim, Kyung-Hee Kim, Jeong-Ah Shin, Kun-Ho Yoon, Bong-Yun Cha, Ho-Young Son, Jae-Hyoung Cho; Diabetes Metab J. 2013;37(1):72-80. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.72

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Background

The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes.

Methods

In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics.

Results

Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment.

Conclusion

Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.

Citations

Citations to this article as recorded by

Predictive clinical parameters for the hemoglobin A1c-lowering effect of vildagliptin in Japanese patients with type 2 diabetes
Yukihiro Bando, Masayuki Yamada, Keiko Aoki, Hideo Kanehara, Azusa Hisada, Kazuhiro Okafuji, Daisyu Toya, Nobuyoshi Tanaka
Diabetology International.2014; 5(4): 229. CrossRef
The Efficacy of Vildagliptin in Korean Patients with Type 2 Diabetes
Jun Sung Moon, Kyu Chang Won
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