J Diabetes Investig. 2016 May;7(3):386-95. doi: 10.1111/jdi.12430. Epub 2015 Nov 12.

Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

Kanatsuka A1, Sato Y2, Kawai K3, Hirao K4, Kobayashi M5, Kashiwagi A6, Japan Diabetes Clinical Data Management Study Group (JDDM): Abe N, Arai K, Fujiya H, Fukumoto Y, Dake F, Iizumi T, Ito M, Iwasaki K, Kanamori A, Kato S, Kato M, Kawara A, Kimura K, Chikamori K, Iemitsu K, Kou S, Kudo M, Kurihara Y, Lee G, Tsuruoka A, Manda N, Matoba K, Hayashi H, Minami M, Kuribayashi N, Miyazawa K, Chiba Y, Osonoi T, Nakamura S, Sasaki H, Komori K, Oishi M, Okada A, Okuguchi F, Yanagisawa M, Sugimoto H, Sugiyama H, Takai M, Takaki M, Takamura H, Takeda H, Takeda H, Tanaka K, Miwa T, Tomonaga O, Taguchi M, Yamazaki K, Wada T, Yagi N, Yamaoka K, Yuhara A.

  • 1Diabetes Center Chiba Central Medical Center Chiba Japan.

 

Abstract

AIMS/INTRODUCTION:

We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics.

MATERIALS AND METHODS:

We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors.

RESULTS:

HbA1c was reduced with all drugs, with the largest effect elicited by DPP-4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age-of-onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of 8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00).

CONCLUSIONS:

The effect on bodyweight and glycemic control differed among metformin, DPP-4i and SU, and the difference was associated with clinical features.

KEYWORDS:

Oral antidiabetic drug; Propensity scorematched cohort study; Type 2 diabetes mellitus

PMID: 27330726

 

Supplement: 

The majority of patients with type 2 diabetes mellitus require oral antidiabetic drugs (OADs) in addition to lifestyle intervention. Recent systematic reviews and meta-analyses1,2, which analyzed data mainly obtained from randomized control trials (RCTs), showed similar drug efficacy and reduction in HbA1c levels by an average of 1 percentage point (1%) across most of the diabetes medications.

Evidence-based medicine is classified according to “grades of evidence” built into the research design3. The highest grade is reserved for research involving “at least one properly randomized controlled trial,” whereas observational studies fall within the intermediate grades4. Recent reviews showed that findings from RCTs and observational studies were similar across several clinical topics, indicating that evidence from both study types can and should be used to find the optimal treatment regimen5,6. However, results obtained from cohort studies are liable to be more affected by biases and confounding baseline factors that might influence treatment selection. One approach to reduce or eliminate the effect of treatment selection bias and confounding effects is the use of the propensity score matching method 9,10

To more robustly examine the relationship between the efficacy of three widely used OADs, metformin (Met), dipeptidyl peptidase-4 inhibitor (DPP-4i) and sulfonylurea (SU), and the patients’ clinical features, we used the CoDiC database collected from 67 institutions across Japan (Fig.1)7,8, analyzed cohort study results that were stratified according to a specific clinical feature and then matched by the propensity score matching method.

 

 

fig-1-kanatsuka

Fig.1 In 2001, the Japan Diabetes Clinical Data Management Study Group (JDDM) was established to promote clinical research into diabetes in Japan7,8. Patient clinical data from Japanese healthcare institutes specializing in diabetes were collated in the CoDiC database, which is a diabetes data collection and management information system developed by the JDDM.

 

In the 3,943 drug-naive patients, Met, DPP-4i, and SU were prescribed in 1793, 877 and 1273 patients, respectively, from May 2007 to July 2012. BMI at the start of drug was higher on Met, and HbA1c was higher on SU. In 1,323 cases matched by propensity scoring for the following characteristics: age, age-of-onset, duration of diabetes, BMI, BP, PPPG, HbA1c and lipids, there were no differences in most variables. HbA1c levels were not different among drugs at the time of initiation, but subsequently, the reduction in HbA1c was largest on DPP-4i and lower on SU.

We next measured changes in BMI or HbA1c in the patients stratified by age-of-onset, duration of this disease, BMI and HbA1c levels at the start of drug therapy, and then matched these patients by propensity scores for the characteristics described earlier. We obtained the results shown in Table 1.

As the comments shown in Table 2, the efficacy on bodyweight and glycemic control differed among Met, DPP-4i and SU, and the differences were related to the clinical features. The data both from our present observational study and from the RCTs potentially apply to all clinical situations of diabetes care.

 

Table 1. Results in the patients stratified by age-of-onset, duration of this disease, BMI and HbA1c levels at the start of drug therapy, and then matched these patients by propensity scores

tab1

Table 2. Comments on the relationship between the efficacy of oral anti-diabetic drug and clinical features

tab2

 

 

References: 

  1. Sherifali D, Nerenberg CK, Pullenayegum E, et al. The effect of oral antidiabetic agents on A1C levels. Diabetes Care 2010; 33: 1859–1864.
  2. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 2011; 154: 602–613.
  3. Evidence-Based Medicine Working Group. Evidence-based medicine: a new approach to teaching the practice of medicine. JAMA 1992; 268: 2420–2425.
  4. Preventive Services Task Force. Guide to clinical preventive services: report of the U.S. Preventive Services Task Force. 2nd ed. Baltimore: Williams & Wilkins, 1996
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  7. Kobayashi M, Yamazaki K, Hirao K, Japan Diabetes Clinical Data Management Study Group, et al. The status of diabetes control and antidiabetic drug therapy in Japan—a cross-sectional survey of 17,000 patients with diabetes mellitus (JDDM1). Diab Res Clin Pract. 2006;73:198–204.
  8. Kanatsuka A, Kawai K, Hirao K, et al. The initiation of insulin therapy in type 2 diabetic patients treated with oral antidiabetic drugs: an observational study in multiple institutes across Japan (JDDM 27). Diabetol Int 2012; 3: 164–173.
  9. Austin CP. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011; 46: 399–424.
  10. Kanatsuka1 A, Sato Y, Kawai K, et al. Evaluation of insulin regimens as an effective option for glycemic control in patients with type 2 diabetes: a propensity score-matched cohort study across Japan (JDDM31). J Diabetes Investig 2014; 5: 539–549.

 

Acknowledgements

This study was supported by a grant from the Japan Diabetes Foundation.

 

Contact:

Azuma Kanatsuka M.D.

Diabetes Centre, Chiba Central Medical Center, Chiba, Japan

E-mail address: azumaka@yahoo.co.jp

 

 

 

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