Originl Article Dibetes Metb J 211;35:26-33 doi: 1.493/dmj.211.35.1.26 pissn 2233-679 eissn 2233-687 D I A B E T E S & M E T A B O L I S M J O U R N A L Comprison of the Efficcy of Glimepiride, Metformin, nd Rosiglitzone Monotherpy in Koren Drug-Nïve Type 2 Dibetic Ptients: The Prcticl Evidence of Antidibetic Monotherpy Study Kun Ho Yoon 1, Jeong Ah Shin 1, Hyuk Sng Kwon 1, Seung Hwn Lee 1, Kyung Wn Min 2, Yu Be Ahn 1, Soon Jib Yoo 1, Kyu Jeung Ahn 3, Sung Woo Prk 4, Kwn Woo Lee 5, Yeon Ah Sung 6, Te Sun Prk 7, Min Seon Kim 8, Yong Ki Kim 9, Moon Suk Nm 1, Hye Soon Kim 11, Ie Byung Prk 12, Jong Suk Prk 13, Jeong Tek Woo 14, Ho Young Son 1 1 Deprtment of Endocrinology, The Ctholic University of Kore School of Medicine, Seoul, 2 Deprtment of Internl Medicine, Eulji University School of Medicine, Dejeon, 3 Deprtment of Endocrinology, Kyung Hee Est-West Neo Medicl Center, Seoul, 4 Deprtment of Internl Medicine, Sungkyunkwn University School of Medicine, Seoul, 5 Deprtment of Endocrinology, Ajou University School of Medicine, Suwon, 6 Deprtment of Endocrinology, Ewh Womn s University School of Medicine, Seoul, 7 Deprtment of Internl Medicine, Chonbuk Ntionl University Hospitl, Jeonju 8 Deprtment of Internl Medicine, University of Ulsn College of Medicine, Seoul, 9 Deprtment of Internl Medicine, Pusn Ntionl University School of Medicine, Busn, 1 Deprtment of Internl Medicine, Inh University College of Medicine, Incheon, 11 Deprtment of Internl Medicine, Keimyung University School of Medicine, Degu, 12 Deprtment of Endocrinology, Gchon University of Science & Medicine, Incheon, 13 Deprtment of Internl Medicine, Yonsei University College of Medicine, Seoul, 14 Deprtment of Endocrinology, Kyung Hee University College of Medicine, Seoul, Kore Bckground: Although mny nti-dibetic drugs hve been used to control hyperglycemi for decdes, the efficcy of commonly-used orl glucose-lowering gents in Koren type 2 dibetic ptients hs yet to be clerly demonstrted. Methods: We evluted the efficcy of glimepiride, metformin, nd rosiglitzone s initil tretment for drug-nïve type 2 dibetes mellitus ptients in 48-week, double-blind, rndomized controlled study tht included 349 Koren ptients. Our primry gol ws to determine the chnge in HbA1c levels from bseline to end point. Our secondry gol ws to evlute chnges in fsting plsm glucose (FPG) levels, body weight, frequency of dverse events, nd the proportion of prticipnts chieving trget HbA1c levels. Results: HbA1c levels decresed from 7.8% to 6.9% in the glimepiride group (P<.1), from 7.9% to 7.% in the metformin group (P<.1), nd from 7.8% to 7.% (P<.1) in the rosiglitzone group. Glimepiride nd rosiglitzone significntly incresed body weight nd metformin reduced body weight during the study period. Symptomtic hypoglycemi ws more frequent in the glimepiride group nd dirrhe ws more frequent in the metformin group. Conclusion: The efficcy of glimepiride, metformin, nd rosiglitzone s ntidibetic monotherpies in drug-nïve Koren type 2 dibetic ptients ws similr in the three groups, with no sttisticl difference. This study is the first rndomized controlled tril to evlute the efficcy of commonly-used orl hypoglycemic gents in Koren type 2 dibetic ptients. An dditionl subgroup nlysis is recommended to obtin more detiled informtion. Keywords: Dibetes mellitus, type 2; Glimepiride; Metformin; Rosiglitzone Corresponding uthor: Ho Young Son Deprtment of Endocrinology & Metbolism, Seoul St. Mry s Hospitl, The Ctholic University of Kore School of Medicine, 55 Bnpo-dong, Seocho-gu, Seoul 137-71, Kore E-mil: hys@ctholic.c.kr Received: Jul. 6, 21; Accepted: Nov. 9, 21 This is n Open Access rticle distributed under the terms of the Cretive Commons Attribution Non-Commercil License (http://cretivecommons.org/licenses/by-nc/3./) which permits unrestricted non-commercil use, distribution, nd reproduction in ny medium, provided the originl work is properly cited. Copyright 211 Koren Dibetes Assocition
The efficcy of ntidibetic monotherpy in Koren INTRODUCTION Type 2 dibetes mellitus is chronic disese chrcterized by incresed insulin resistnce, defective β-cell function, nd incresed heptic gluconeogenesis [1]. The proportion of ptients with type 2 dibetes hs been consistently incresing worldwide, nd recent increses re remrkble in Asi, including Kore [2,3]. Becuse the incresing burden of dibetes cuses substntil finncil loss resulting from incresed helth cre expenditures [4], type 2 dibetes is not personl disese, but is n importnt ntionl public helth problem. For glycemic control, life style interventions with metformin re recommended s n initil tretment regimen in consensus sttement from the Americn Dibetes Assocition [5]. And there hve been mny clinicl trils in Western countries on the selection of n optiml orl hypoglycemic gent for initil tretment [6-8]. In Jpn, Ymnouchi et l. [9] estblished tht severl commonly-used orl hypoglycemic gents were eqully effective in newly-dignosed type 2 dibetic ptients. However, the doses of ech drug were completely different from the usul prescription dosge in Kore, which mkes it hrd to trnslte those dt into clinicl prctice in Kore. Furthermore, there hs been no hed-to-hed comprison in rndomized controlled tril to prove the efficcy nd sfety of ntidibetic gents for Koren type 2 dibetic ptients. This study ws designed to evlute glycemic control efficcy in Koren drug-nïve type 2 dibetic ptients receiving monotherpy with sulfonylure (glimepiride), bigunide (metformin), or thizolidinedione (rosiglitzone). METHODS Study design This study, clled the Prcticl Evidence of Antidibetic Monotherpy Study (PEAM), consisted of multicenter, rndomized, double-blind tril performed in 15 centers in Kore. Between Februry 27 nd December 28, 435 ptients who hd not received previous phrmcologic tretment for type 2 dibetes mellitus were screened nd 349 ptients were rndomized to one of three tretment groups. We ssigned 118 ptients to the glimepiride group, 114 ptients to the metformin group, nd 117 ptients to the rosiglitzone group (Fig. 1). After 4-week life style intervention, the study drugs were prescribed to ech ptient. During the lifestyle intervention period, we provided individulized eduction to ech study subject, ccording to current, recommended guidelines for medicl nutritionl tretment [1]. We lso recommended tht ech subject perform t lest 15 minutes per week of moderte-inten- 435 Screened ptients 86 Excluded ptients 349 Rndomized ptients 118 Glimepiride 114 Metformin 117 Rosiglitzone 36 Withdrwl 8 Poor drug complince 6 Withdrwl of consent 1 Adverse events 5 Loss of follow up 2 Protocol violtion 5 Other reson 43 Withdrwl 9 Poor drug complince 11 Withdrwl of consent 9 Adverse events 9 Loss of follow up 2 Protocol violtion 1 Insufficient response 2 Other reson 43 Withdrwl 13 Poor drug complince 8 Withdrwl of consent 6 Adverse events 5 Loss of follow up 4 Protocol violtion 2 Pregnncy 1 Insufficient response 4 Other reson 82 Study end 71 Study end 74 Study end Fig. 1. Enrollment nd study outcomes. The totl number of ptients ssigned to the three tretment groups ws 349. A totl of 36 ptients left the glimepiride group, 43 left the metformin group, nd 43 left the rosiglitzone group during the study period. Dibetes Metb J 211;35:26-33 27
Yoon KH, et l. sity erobic physicl ctivity, provided exercise ws not contrindicted [1]. Trined dietitins or dibetic nurse specilists provided the eduction nd mde these recommendtions; however, we did not lter verify whether the subjects hd followed these recommendtions ppropritely. Prticipnts were exmined every 8 weeks for 48 weeks from the strt of the rndomiztion period. According to the results of HbA1c (<6.5% or 6.5%) nd drug tolerbility check tht ws performed t ech visit, we performed scheduled up-titrtion of the study drugs (Tble 1A). Fsting plsm glucose levels (FPG), HbA1c concentrtions, mediction complince, nd physicl exmintion, including tking vitl signs nd body weight (BW), were ssessed or performed t every visit. To evlute the study prticipnts mediction complince indirectly, we checked the number of remining doses t ech visit. The rtio of the remining number of doses t the present visit to the number of doses prescribed t the previous visit ws clculted. Subjects with rtio greter thn 3% were excluded in the outcome nlysis, since their complince rte ws presumed to be less thn 7%. At the outset of rndomiztion nd fter 48 weeks, we performed 75 g orl glucose tolernce test. Anthropometric chrcteristics, demogrphic chrcteristics, electrocrdiogrm, lipid profiles, complete blood counts (CBC), sprtte minotrnsferse (AST), lnine minotrnsferse (ALT), blood ure nitrogen (BUN), nd cretinine were evluted. All dverse events were recorded nd judged for severity nd possible reltionship to study medictions. The study protocol ws pproved by the Institutionl Review Bord t ech center nd ll prticipnts provided written informed consent. Study prticipnts Eligible study prticipnts were between the ges of 3 nd 65 yers, with HbA1c levels rnging from 6.5% to 9.5%. None of the subjects hd ever tken n orl hypoglycemic gent. Glucocorticoid users, pregnnt women, ptients who hd cliniclly significnt liver disese (AST, ALT>2.5 x upper norml limit), significnt renl disese (serum cretinine>1.5 mg/dl in men,>1.4 mg/dl in women), history of lctic cidosis, history of unstble ngin or severe ngin pectoris, history of or tretment for congestive hert filure, or contrindictions to metformin or sulfonylure tretment were excluded. Gol ssessment The primry gol of this study ws to determine chnges in HbA1c levels from bseline (rndomiztion) to end point. The secondry gols were to determine chnges in FPG, body Tble 1. Study design (A) Dose titrtion schedules for study drugs Glimepiride (2 mg/t) Metformin (5 mg/t) Rosiglitzone (4 mg/t) AM PM AM PM AM PM Level 1 2 mg 5 mg 4 mg Level 2 2 mg 2 mg 5 mg 5 mg 4 mg Level 3 4 mg 2 mg 1, mg 5 mg 4 mg 4 mg Level 4 4 mg 4 mg 1, mg 1, mg 4 mg 4 mg (B) Drug level t ech visit Glimepiride Metformin Rosiglitzone L1 L2 L3 L4 L1 L2 L3 L4 L1 L2 L3 L4 V1 118 (1) 114 (1) 117 (1) V2 73 (61.9) 45 (38.1) 46 (4.4) 68 (59.6) 44 (38.6) 73 (61.4) V3 62 (52.5) 31 (26.3) 25 (21.2) 4 (35.1) 32 (28.1) 42 (36.8) 41 (35.) 33 (28.2) 43 (36.8) V4 59 (5.) 24 (2.3) 17 (14.4) 18 (15.3) 36 (31.6) 28 (24.5) 31 (27.2) 19 (16.7) 39 (33.3) 29 (24.8) 18 (15.4) 31 (26.5) V5 57 (48.3) 18 (15.3) 17 (14.4) 26 (22.) 36 (31.6) 23 (2.2) 26 (22.8) 29 (25.4) 36 (3.8) 28 (23.9) 16 (13.7) 37 (31.6) V6 55 (46.6) 2 (16.9) 8 (6.8) 35 (29.7) 35 (3.7) 22 (19.3) 25 (21.9) 32 (28.1) 34 (29.1) 25 (21.3) 16 (13.7) 42 (35.9) Vlues re presented s number (%). T, tblet; L, level; V, visit. 28 Dibetes Metb J 211;35:26-33
The efficcy of ntidibetic monotherpy in Koren weight, nd the numbers of subjects chieving trget HbA1c levels (<6.5%). We evluted differences in ll dverse events for the study popultions. Hypoglycemi ws defined s the presence of typicl drenergic or neuroglycopenic symptoms nd signs, regrdless of the dt for self-monitoring of blood glucose. Edem ws defined when the subjects hd ny signs of fluid retention upon physicl exmintion, or complined of systemic edem. At bseline, 24 weeks, nd 48 weeks, HbA1c levels were mesured using high-performnce liquid chromtogrphy nd FPG ws determined using hexokinse method in centrl lbortory (Smkwng Medicl Lbortories, Seoul, Kore). Levels of FPG nd HbA1c in the other follow-up visits, nd lipid levels, were determined using stndrd ssys in ech locl lbortory. Sttisticl nlysis Originlly, we clculted need to enroll 54 study prticipnts to obtin 8% sttisticl power t significnce level of P=.5, ssuming 2% ttrition rte in ech study group. At the end of the study, the overll ttrition rte ws 34.9%, with totl of 349 rndomized subjects. We used n intention-to-tret nlysis method in nlyzing our dt. The lst observtion crried forwrd (LOCF) method ws used to fill in missing vlues t lter point in the study. Using per protocol nlysis, we included, 82 subjects in the glimepiride group, 71 subjects in the metformin group, nd 74 subjects in the rosiglitzone groups in Tble 2. Bseline chrcteristics Vrible Totl (n=349) Glmepiride (n=118) Metformin (n=114) Rosiglitzone (n=117) P vlue Demogrphic chrcteristics Age, yr 5.9±8.5 5.8±8.9 51.8±8.5 5.1±8.2.23 Mles, n (%) 193 (55.3) 66 (55.93) 66 (57.89) 61 (52.14).67 Anthropometric chrcteristics Weight, kg 68.7±11.4 67.9±1.9 68.9±11.1 69.1±12. 1.69 BMI, kg/m 2 25.6±3.2 25.5±3.1 25.7±3.2 25.8±3.3.63 Wist circumference, cm 87.6±7.9 87.±7.8 88.7±7.2 87.6±7.9.18 Hip circumference, cm 97.1±6.3 96.2±5.6 97.5±6.1 97.1±6.3.21 Wist-to-hip rtio.9±.5.91±.5.91±.5.89±.5.1 Blood pressure Systolic, mm Hg 127.2±13.2 126.3±12.8 128.2±12.4 127.±14.4.62 Distolic, mm Hg 78.9±9.4 78.4±8.7 79.8±8.6 78.8±1.7.48 Antihypertensive therpy, n (%) 12 (29.23) 34 (28.81) 33 (28.95) 35 (29.91).98 Lipid-lowering therpy, n (%) 99 (28.37) 35 (29.66) 33 (28.95) 31 (26.5).85 Metbolic chrcteristics FBS, mg/dl 146.6±32. 145.±32. 151.±32.4 144.1±31.5.1 HbA1c, % 7.8±.8 7.8±.8 7.9±.8 7.8±.8.29 Totl cholesterol, mg/dl 189.1±37.5 19.2±41.3 186.8±34.3 19.4±36.7.72 Triglyceride, mg/dl 134.±18. 127.±114. 144.±99. 141.±119..69 b HDL-C, mg/dl 45.±13. 45.±12. 43.±13. 47.±14..47 b LDL-C, mg/dl 19.2±37. 11.9±42. 16.±33.7 11.4±34.6.54 TC/HDL rtio 4.16±1.62 4.3±1.61 4.18±1.52 4.24±1.8.88 b TG/HDL rtio 2.87±2.96 2.85±2.79 3.18±2.89 2.79±3.31.59 b Dt re presented s men±stndrd devition, except where vrible is mrked with n symbol. HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, totl cholesterol; TG, triglyceride. Dt re presented s medin±interqurtile rnge, b Kruskl-Wllis test ws used for nonprmetric sttisticl nlysis nd ANOVA test for prmetric nlysis. Dibetes Metb J 211;35:26-33 29
Yoon KH, et l. our nlysis (dt not shown here). Results re described s men ±stndrd devition or medin±interqurtile rnge. For comprisons of dt mong the three tretment groups, repeted mesured ANOVA test ws used. For nonprmetric sttisticl nlysis, the Kruskl- Wllis test ws used. Wilcoxon s signed rnk test ws used for comprison of pre- nd post-tretment vlues. For nlysis of differences in the frequency of dverse events, the chi-squre test nd Fisher s exct test were used. Sttisticl nlyses were performed using SAS version 9.1.3 (SAS Institute, Cry, NC, USA). Differences mong groups with P<.5 were considered sttisticlly significnt. RESULTS Bseline nd follow-up chrcteristics The subjects bseline chrcteristics re described in Tble 2. All vribles in bseline chrcteristics were mesured t the rndomiztion point. There ws no significnt difference in HbA1c levels, body weight, blood pressure, nd lipid profiles between the screening visit nd the rndomiztion visit (dt from the screening period not shown here). The men ge of the totl study popultion ws 5.9 yers, the men HbA1c level ws 7.8%, nd the men body mss index (BMI) ws 25.6 kg/m 2. No significnt difference ws observed in bseline demogrphics, nthropometrics nd metbolic chrcteristics mong the three groups fter rndomiztion. Mediction complince ws not different in the three groups. The proportion of prticipnts who completed the study ws 69.4% in the glimepiride group, 62.3% in the metformin group, nd 63.2% in the rosiglitzone group. The number of study prticipnts t ech drug dosge level is described in Tble 1B. Primry outcome HbA1c levels decresed from 7.8% to 6.9% in the glimepiride group (P<.1), from 7.9% to 7.% in the metformin group (P<.1), nd from 7.8% to 7.% (P<.1) in the rosiglitzone group (Fig. 2). Differences in HbA1c levels from rndomiztion to the end point were -.89±.76% in the glimepiride group, -.92±.96% in the metformin group, nd -.82±.79% in the rosiglitzone group. There ws no significnt difference in the HbA1c levels, or in the chnges in HbA1c levels, between the three groups (P=.62) (Fig. 3A). Secondry outcome Levels of FPG decresed from 145.±32. mg/dl to 128.1± 27.9 mg/dl in the glimepiride group (P<.1), from 151.± 32.4 mg/dl to 13.8±25.8 mg/dl in the metformin group (P<.1), nd from 144.1±31.5 mg/dl to 128.6±35.2 mg/dl in the rosiglitzone group (P<.1). Among the three study groups, levels of FPG t bseline nd the end point were sttisticlly different (P=.52) (Fig. 3B). Over the study period, significnt weight gin ws observed in the glimepiride group (ΔBW=1.4 kg, ΔBMI=.54 kg/m 2 ). In the rosiglitzone group, men weight incresed continuously (ΔBW=1.5 kg, ΔBMI=.63 kg/m 2 ); however there ws significnt weight reduction in the metformin group (ΔBW= -1.1 kg, ΔBMI=-.44 kg/m 2 ) (Fig. 3C). Study prticipnts chieving trget HbA1c levels of less thn 6.5% were 36.44% (43 subjects) of the 118 members of the glimepiride group, 24.56% (28 subjects) of the 114 members of the metformin group, nd 32.48% (38 subjects) in the 117 members of the rosiglitzone group, without significnt differences mong the three groups (P=.14). Those with HbA1c level less thn 7.% were 65.25% (77 subjects) of the glimepiride group, 58.77% (67 subjects) of the metformin group, nd 58.97% (69 subjects) of the rosiglitzone group, with no significnt differences mong the three groups (P=.51) (Fig. 4). HbA1c (%) 9 8 7 6 7.8 7.9 7.8 6.9 7. 7. Glimepiride Metformin Rosiglitzone -.89±.76 -.92±.96 -.82±.79 4.5 mg 1,234.2 mg 5.9 mg Fig. 2. Chnges in HbA1c from bseline to end point. The blck br indictes the HbA1c level t bseline nd gry br t end point. Brs represent men + stndrd devition. Significnt differences between HbA1c t week nd 48 weeks (P vlue<.1). Repeted mesured ANOVA test ws used for sttisticl nlysis. Between the three groups, HbA1c levels nd chnges were not sttisticlly different (P vlue=.62). HbA1c Men doses t end point 3 Dibetes Metb J 211;35:26-33
The efficcy of ntidibetic monotherpy in Koren 8 155 HbA1c (%) 7.6 7.2 6.8 * FPG (mg/dl) 145 135 125 Body weight (kg) 8 16 24 32 4 48 Time (wk) A 74 72 7 68 66 8 16 24 32 4 48 Time (wk) C 8 16 24 32 4 48 Time (wk) B Glimepiride group Metformin group Rosiglitzone group Fig. 3. Chnges in HbA1c (A), fsting plsm glucose (FPG) (B), nd body weight (C) over time, by tretment group. All pnels, dt re presented s men±stndrd error of men. Significnt differences between the three tretment groups (P vlue<.5). % 7 6 5 4 3 2 1 65.25 36.44 58.77 24.56 P vlue=.51 P vlue=.14 58.97 32.48 Glimepiride Metformin Rosiglitzone (n=118) (n=114) (n=117) Fig. 4. Proportion of ptients chieving trget HbA1c levels. Blck br indictes the proportion of ptients chieving HbA1c levels less thn 7.% nd white br less thn 6.5%. The χ 2 test ws used for comprison of differences in the three groups. Adverse events Symptomtic hypoglycemi ws more frequent in the glimepiride group (19.49% in glimepiride group vs. 3.51% in metformin group nd 6.84% in rosiglitzone group). Dirrhe ws more frequent in the metformin group (3.39% of glimepiride group vs. 8.77% of metformin group nd 1.71% of rosiglitzone group). Subjective edem s reported by study prticipnts ws more frequent in the glimepiride nd rosiglitzone groups compred to the metformin group (6.78% of glimepiride group vs..88% of metformin group nd 7.69% of rosiglitzone group) (Tble 3). Other dverse events, including bdominl discomfort, elevted liver enzymes nd chest discomfort or dyspne were not different in the three study popultions. DISCUSSION The three study drugs similrly decresed HbA1c levels by.8-.9% by the end of the study. In mny previous plcebo-controlled trils, glimepiride, metformin, nd rosiglitzone lowered HbA1c levels by bout 1.-1.5% [11-13]. The differences between our results nd previous studies might be influenced by bseline HbA1c levels, BMI, nd prescribed doses of the study drugs. Previous reports in western countries noted prticipnt Dibetes Metb J 211;35:26-33 31
Yoon KH, et l. Tble 3. Adverse events Adverse event Rosiglitzone (n=117) Glimepiride (n=118) Metformin (n=114) P vlue Edem 9 (7.69) 8 (6.78) 1 (.88).4 b,c Elevted liver enzymes Symptomtic hypoglycemi Abdominl discomfort & pin including nuse, vomiting 1 (.85) 5 (4.24) (.).5 8 (6.84) 23 (19.49) 4 (3.51).,b 15 (12.82) 1 (8.47) 1 (8.77).47 Dirrhe 2 (1.71) 4 (3.39) 1 (8.77).3 b,c Chest discomfort & dyspne 3 (2.56) 3 (2.54) 7 (6.14).28 Totl 38 (32.48) 53 (44.92) 32 (28.7) Dt re presented s number (%)., b, nd c indicte significnt difference between two groups. glimepiride vs. rosiglitzone, b glimepiride vs. metformin, c rosiglitzone vs. metformin. χ 2 test nd Fisher s exct test were used for comprison of differences in the three groups. bseline HbA1c levels 8.5-1% nd BMIs of 26-3 kg/m 2 [12, 13], wheres our study prticipnts hd HbA1c levels nd BMIs of 7.8% nd 25 kg/m 2, respectively. We infer these different results my be due to our study popultion hving reltively mild hyperglycemi nd lower BMIs. At the end of the study, the ttrition rte ws higher thn expected (34.9% vs. 2.%). Therefore, the relibility of our tril ws lower thn originlly estimted t the point of study design. The fstest response of HbA1c nd FPG to the study drugs ws observed in study prticipnts receiving glimepiride in the first 24 weeks. This slower ction in reducing blood glucose levels using metformin nd rosiglitzone, s compred to glimepiride, is similr to previous report [14]. The mximum hypoglycemic effect ws seen t 32 weeks in the glimepiride nd rosiglitzone groups nd t 4 weeks in the metformin group; therefore, n observtionl period t lest 6 to 8 months ppers to be needed to judge whether ptient is responding to specific orl ntihyperglycemic drug. Although bout 6% of the study prticipnts reched trget HbA1c level of less thn 7.%, the rest of the study prticipnts remined in n indequte glycemic control stte. And only bout 3% of the subjects reched trget HbA1c less thn 6.5%. To improve the stte of ptients glycemic control, more ctive tretment should be performed nd dditionl studies nd nlyses re needed to elucidte severl fctors influencing the level of glycemic control. Wheres metformin does not cuse weight gin nd my induce modest weight loss in type 2 dibetic ptients, glimepiride nd rosiglitzone generlly result in weight gin [15-17]. In this study, metformin induced significnt weight loss, while glimepiride nd rosiglitzone induced significnt weight gin in Koren type 2 dibetic ptients. This suggests useful nd beneficil helth effect to using metformin for obese or overweight Koren dibetic ptients. As in previous studies [18], the most common side effect ws symptomtic hypoglycemi in the glimepiride group. Although metformin nd rosiglitzone re not known to induce hypoglycemi [19,2], few study prticipnts in those groups complined of hypoglycemic symptoms; however, these complints cnnot be confirmed s true hypoglycemi, s our study did not involve self-monitoring of blood glucose levels t the time the study prticipnts felt hypoglycemic symptoms. The min dverse event with metformin ws dirrhe; with rosiglitzone, it ws edem due to fluid retention nd weight gin. Overll, 8-12% of study prticipnts experienced bdominl disturbnces including pin, discomfort, nuse, or vomiting during the study period; however, the symptoms were trnsient in the mjority of the study prticipnts nd the cusl reltionship between the study drugs nd symptoms is uncertin. We did not ssess ctul chnges in lipid prmeters during the study due to use of dditionl nti-hyperlipidemic gents. Lipid prmeters re importnt in understnding secondry effects of the study drugs nd re chngeble ccording to the gents used [9,21]. Future studies should be designed to evlute the true effects of ntihyperglycemic gents on lipid prmeters in Koren ptients. In conclusion, this study demonstrtes tht the efficcies of glimepiride, metformin, nd rosiglitzone re similr, with no sttisticl differences, when used for ntidibetic monotherpy in drug-nïve type 2 dibetic ptients. This tril is the first rndomized controlled tril to evlute the efficcy of commonly-used ntidibetic gents in Koren type 2 dibetic ptients. Specific chrcteristics of the study drugs should be considered when choosing n pproprite gent. To use these results s vluble informtion for selecting n orl hypoglycemic gent, more detiled subgroup nlyses nd further investigtion is recommended. 32 Dibetes Metb J 211;35:26-33
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