Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus.

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Term Occurence Count Dictionary
pioglitazone 7 endocrinologydiseasesdrugs
rosiglitazone 3 endocrinologydiseasesdrugs
sitagliptin 3 endocrinologydiseasesdrugs
type 2 diabetes mellitus 5 endocrinologydiseases
hypoglycemia 17 endocrinologydiseases
metformin 71 endocrinologydiseasesdrugs
Insulin 1 endocrinologydiseasesdrugs
acarbose 4 endocrinologydiseasesdrugs
dapagliflozin 1 endocrinologydiseasesdrugs
diabetes mellitus 5 endocrinologydiseases
diabetic ketoacidosis 1 endocrinologydiseases
glyburide 1 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Insulin 25158 resulted in significant additional mean reductions in HbA1c from –0.56% (DPP4i) to –0.94% (TZDs). Insulin , TZD and SU were associated with less favourable weight change and GLP-1RA and SGLT2i were associated
acarbose 15408 consistently better when combined with TZD (–0.93%) and SGLT2i (–0.86%) than with DPP4i (–0.68%) or acarbose (–0.60%). When triple therapies are compared with each other; however, there are no statistically
acarbose 15746 randomized controlled trials, canagliflozin and TZDs reduced HbA1c by ~1% (range, 0.98% to 1.2%), whereas acarbose , dapagliflozin, empagliflozin, and DPP4i reduced HbA1c by 0.60% to 0.76% when compared to placebo/control
acarbose 18059 in metformin add-on and in metformin + SU add-on, SGLT2i and TZD showed more efficacy than DPP4i or acarbose , but the actual difference was as small as 0.1% to 0.2% of HbA1c. Although the difference is statistically
acarbose 23282 placebo/control, all antihyperglycemic agents reduced HbA1c levels, albeit by differing magnitudes (0.6% for acarbose to 1.20% for liraglutide)SGLT2i reduced weight (1.43–2.07 kg), whereas TZDs, glargine and sitagliptin
dapagliflozin 15756 controlled trials, canagliflozin and TZDs reduced HbA1c by ~1% (range, 0.98% to 1.2%), whereas acarbose, dapagliflozin , empagliflozin, and DPP4i reduced HbA1c by 0.60% to 0.76% when compared to placebo/control [[44]]. Interestingly,
glyburide 14708 incidence of monotherapy failure at 5 years was 15% with rosiglitazone, 21% with metformin, and 34% with glyburide [[38]]. Therefore, it is difficult to say that either DPP4i or TZD is superior, and appropriate drugs
metformin 1034 trials on Korean patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were
metformin 1047 patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different.
metformin 1202 each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the
metformin 1247 different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the patient’s clinical characteristics and the
metformin 3442 antihyperglycemic agents1. Metformin is the preferred initial oral antihyperglycemic agent [A].2. If metformin is contraindicated or intolerable as the initial treatment, then another class of antihyperglycemic
metformin 4637 ADD-ON THERAPY TO METFORMIN?There are six major classes of antidiabetic agents that can be combined with metformin . They are sulfonylurea (SU), thiazolidinediones (TZDs), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose
metformin 5437 OHAs based on meta-analyses and suggest a guide to select one as a first-combination medication with metformin .Comparison of SU and DPP4i as an add-on therapy to metforminSeveral meta-analyses compared SU and DPP4i
metformin 5498 as a first-combination medication with metformin.Comparison of SU and DPP4i as an add-on therapy to metformin Several meta-analyses compared SU and DPP4i as an add-on therapy to metformin [[6]-[11]]. DPP4i lowered
metformin 5575 as an add-on therapy to metforminSeveral meta-analyses compared SU and DPP4i as an add-on therapy to metformin [[6]-[11]]. DPP4i lowered HbA1c levels to a similar extent [[6],[7]] or slightly less (HbA1c difference
metformin 5749 [[6],[7]] or slightly less (HbA1c difference 0.08% to 0.21%) [[8],[9],[11]] compared to SU when added to metformin (Table 1). A meta-analysis comparing DPP4i with SU as an add-on therapy to metformin showed a significantly
metformin 5834 when added to metformin (Table 1). A meta-analysis comparing DPP4i with SU as an add-on therapy to metformin showed a significantly greater reduction in HbA1c from baseline to 12 weeks with SU versus DPP4i (mean
metformin 6366 CV mortality, all-cause mortality, serious adverse events, or myocardial infarction, but DPP4i and metformin exhibited a lower risk of stroke compared with a combination of SU and metformin (OR, 0.47; 95% confidence
metformin 6447 infarction, but DPP4i and metformin exhibited a lower risk of stroke compared with a combination of SU and metformin (OR, 0.47; 95% confidence interval [CI], 0.23 to 0.95) in a meta-analysis of 301 randomized clinical
metformin 6778 using the Korean National Health Insurance Service (NHIS) claims database, however, treatment with SU + metformin was associated with increased total cardiovascular disease (CVD) (hazard ratio [HR], 1.20; 95% CI, 1.09
metformin 7041 CI, 1.04 to 1.91), and ischemic stroke risks (HR, 1.51; 95% CI, 1.28 to 1.79) compared with a DPP4i + metformin regimen [[12]]. Because there is no randomized controlled prospective study for CV outcomes for SU,
metformin 7429 terms of efficacy and superior in terms of safety.Comparison of SU and SGLT2i as an add-on therapy to metformin Two meta-analyses showed that SGLT2i as an add-on therapy to metformin lowered HbA1c levels more (0.15%)
metformin 7499 SGLT2i as an add-on therapy to metforminTwo meta-analyses showed that SGLT2i as an add-on therapy to metformin lowered HbA1c levels more (0.15%) than SU did (Table 2) [[6],[13]-[16]]. In addition, SGLT2i was associated
metformin 8198 and −1.5 kg (baseline, 72.1 kg) with empagliflozin 10 and 25 mg, respectively, when combined with metformin in Asian patients with T2DM [[18]]. These results were consistent with previous empagliflozin phase
metformin 8525 empagliflozin 10 mg, and −0.77% ± 0.05% with empagliflozin 25 mg [[19]]. In terms of ipragliflozin and metformin combination therapy in Korean patients with T2DM inadequately controlled with metformin, adjusted mean
metformin 8613 ipragliflozin and metformin combination therapy in Korean patients with T2DM inadequately controlled with metformin , adjusted mean differences versus placebo in change from baseline in HbA1c were −0.60% (baseline,
metformin 8914 results suggested that the efficacy of SGLT2i in Korean patients with T2DM as an add-on therapy to metformin would be similar to Caucasian populations.Comparison of DPP4i and SGLT2i as an add-on therapy to metforminA
metformin 9021 metformin would be similar to Caucasian populations.Comparison of DPP4i and SGLT2i as an add-on therapy to metformin A meta-analysis of 4 clinical studies showed that SGLT2i as an add-on therapy to metformin lowered HbA1c
metformin 9111 therapy to metforminA meta-analysis of 4 clinical studies showed that SGLT2i as an add-on therapy to metformin lowered HbA1c levels more (0.17%) and body weight much more than DPP4i (Table 3) [[13],[21]-[24]]. In
metformin 12272 comprehensive answer about whether SGLT2i or DPP4i should be preferable in combination therapy with metformin . The choice of an adequate drug should be decided in consideration of the individual characteristics
metformin 12485 the patient and the response to the drug.Comparison of TZD and SU or DPP4i as an add-on therapy to metformin A meta-analysis showed that TZD lowered HbA1c levels to similarly to SU and slightly more (0.12%) than
metformin 12617 that TZD lowered HbA1c levels to similarly to SU and slightly more (0.12%) than DPP4i when added to metformin [[6]]. TZD significantly increased body weight compared to SU and DPP4i [[6]]. This meta-analysis included
metformin 13126 vildagliptin (50 mg twice daily) to that of pioglitazone (15 mg once daily) as an add-on treatment to metformin in Korean patients with T2DM, the efficacy of vildagliptin to lower the HbA1c level was not inferior
metformin 13469 the other hand, in the study comparing the efficacy of lobeglitazone and pioglitazone as add-ons to metformin , both of them decreased HbA1c by 0.74% at week 24 [[36]]. Therefore, the efficacy difference between
metformin 14030 of 349,476 patients with T2DM, using the Korean NHIS claims database, treatment with pioglitazone + metformin was associated with decreased total CVD (HR, 0.89; 95% CI, 0.81 to 0.99), ischemic stroke risks (HR,
metformin 14261 to 0.99), and increased heart failure risks (HR, 4.81; 95% CI, 3.53 to 6.56) compared with a DPP4i + metformin combination [[12]]. It has been reported that TZDs have long-term benefits in glycemic control by augmenting
metformin 14684 T2DM, the cumulative incidence of monotherapy failure at 5 years was 15% with rosiglitazone, 21% with metformin , and 34% with glyburide [[38]]. Therefore, it is difficult to say that either DPP4i or TZD is superior,
metformin 15050 to evaluate the comparative effectiveness and safety of triple combination therapy (drugs added to metformin + SU) (Table 4) [[8],[41]-[44]]. The addition of a third drug to metformin + SU therapy was statistically
metformin 15125 therapy (drugs added to metformin + SU) (Table 4) [[8],[41]-[44]]. The addition of a third drug to metformin + SU therapy was statistically and clinically more effective at reducing HbA1c than dual therapy with
metformin 15237 SU therapy was statistically and clinically more effective at reducing HbA1c than dual therapy with metformin + SU. In these analyses, the HbA1c-lowering effect was consistently better when combined with TZD (–0.93%)
metformin 15908 HbA1c by 0.60% to 0.76% when compared to placebo/control [[44]]. Interestingly, a triple combination of metformin + TZD + DPP4i showed no improvement in HbA1c compared to metformin + SU [[41]]. In terms of weight,
metformin 15975 Interestingly, a triple combination of metformin + TZD + DPP4i showed no improvement in HbA1c compared to metformin + SU [[41]]. In terms of weight, as we can expect, the SGLT2i was associated with significant weight
metformin 16289 terms of hypoglycemia, although the results are different among the analyses, TZDs as add-on therapy to metformin + SU were associated with significantly higher rates of hypoglycemia [[8],[44]]. It seems there are
metformin 16759 between any of the drug classes given as triple therapy [[8]]. From these analyses, the combination of metformin + SU + TZD is the best in lowering HbA1c, but it is the worst in weight gain and hypoglycemia. The combination
metformin 16883 the best in lowering HbA1c, but it is the worst in weight gain and hypoglycemia. The combination of metformin + SU + SGLT2i is the second-best in lowering HbA1c, but it is the best in weight loss. The combination
metformin 16999 SGLT2i is the second-best in lowering HbA1c, but it is the best in weight loss. The combination of metformin + SU + DPP4i is relatively weak in lowering HbA1c compared to metformin + SU + SGLT2i or metformin +
metformin 17071 weight loss. The combination of metformin + SU + DPP4i is relatively weak in lowering HbA1c compared to metformin + SU + SGLT2i or metformin + SU + TZD. Therefore, SGLT2i is a reasonable option as a third agent added
metformin 17098 metformin + SU + DPP4i is relatively weak in lowering HbA1c compared to metformin + SU + SGLT2i or metformin + SU + TZD. Therefore, SGLT2i is a reasonable option as a third agent added to metformin + SU. At this
metformin 17187 SGLT2i or metformin + SU + TZD. Therefore, SGLT2i is a reasonable option as a third agent added to metformin + SU. At this point, we have to consider that the efficacy of DPP4i can be higher in Asians. Actually,
metformin 17456 levels (0.87% at week 24) compared with placebo in 219 Korean patients inadequately controlled with metformin and glimepiride [[45]]. In the other study, the addition of vildagliptin to metformin and SU decreased
metformin 17542 controlled with metformin and glimepiride [[45]]. In the other study, the addition of vildagliptin to metformin and SU decreased the adjusted mean HbA1c levels by 1.19% at week 24 [[32]], and this reduction seems
metformin 17834 about the comparison of other triple combination therapies other than the addition of a third drug to metformin + SU, the preceding descriptions about triple combination therapy need to be interpreted with care.CONCLUSIONSBoth
metformin 17962 preceding descriptions about triple combination therapy need to be interpreted with care.CONCLUSIONSBoth in metformin add-on and in metformin + SU add-on, SGLT2i and TZD showed more efficacy than DPP4i or acarbose, but
metformin 17986 triple combination therapy need to be interpreted with care.CONCLUSIONSBoth in metformin add-on and in metformin + SU add-on, SGLT2i and TZD showed more efficacy than DPP4i or acarbose, but the actual difference was
metformin 18914 of meta-analyses reviewed for comparison of sulfonylurea and DPP-4 inhibitor as an add-on therapy to metformin StudyIncluded trials (n)ResultsPalmer et al. (2016) [[8]]301 RCTs comparing 2 glucose-lowering drug classes
metformin 19313 combination) and the risk of cardiovascular or all-cause mortalityAll drugs were effective when added to metformin .Mishriky et al. (2015) [[7]]16 RCTs comparing DPP4i to SU as add-on therapy to metforminA significantly
metformin 19402 when added to metformin.Mishriky et al. (2015) [[7]]16 RCTs comparing DPP4i to SU as add-on therapy to metformin A significantly greater reduction in HbA1c from baseline to 12 weeks with SU vs. DPP4i (MD, 0.21%; 95%
metformin 20623 AE and hypoglycemia.Foroutan et al. (2016) [[10]]10 RCTs comparing DPP4i to SU as add-on therapy to metformin (10,139 subjects)DPP4i compared to SU produced a non-significant difference in HbA1c% change whereas
metformin 21318 2.Between-group differences in the change in HbA1c for comparison of SU and SGLT2i as an add-on therapy to metformin [[13]]InterventionTrialsDuration, wkNo. of patientsHbA1c SGLT2iHbA1c controlChange in HbA1c (mean difference)Metformin
metformin 21929 3.Between-group differences in the change in HbA1c for comparison of DPP4i and SGLT2i as an add-on therapy to metformin [[13]]InterventionTrialsDuration, wkNo. of patientsHbA1c SGLT2iHbA1c controlChange of HbA1c (mean difference)Metformin
metformin 22977 combination) and the risk of cardiovascular or all-cause mortalityAll drugs were effective when added to metformin .Mearns et al. (2015) [[44]]20 RCTs evaluating 13 antihyperglycaemic agents in adults with T2DM experiencing
metformin 23135 antihyperglycaemic agents in adults with T2DM experiencing poor glycemic control despite optimized metformin and SU therapyCompared with placebo/control, all antihyperglycemic agents reduced HbA1c levels, albeit
metformin 24026 tract infection by 3.9-fold compared with placebo/control.Downes et al. (2015) [[41]]27 RCTs comparing metformin + SU dual therapy to other triple therapy combinationsFor HbA1c reduction, all triple therapies were
metformin 24163 triple therapy combinationsFor HbA1c reduction, all triple therapies were statistically superior to metformin + SU dual therapy, except for metformin + TZD + DPP4i. None of the triple therapy combinations demonstrated
metformin 24203 reduction, all triple therapies were statistically superior to metformin + SU dual therapy, except for metformin + TZD + DPP4i. None of the triple therapy combinations demonstrated differences in HbA1c compared with
metformin 24367 demonstrated differences in HbA1c compared with other triple therapies.Metformin + SU + SGLT2i and metformin + SU + GLP-1RA resulted in significantly lower body weight than metformin + SU + DPP4i, metformin +
metformin 24441 therapies.Metformin + SU + SGLT2i and metformin + SU + GLP-1RA resulted in significantly lower body weight than metformin + SU + DPP4i, metformin + SU + insulin and metformin + SU + TZDs; metformin + SU + DPP4i resulted in
metformin 24465 and metformin + SU + GLP-1RA resulted in significantly lower body weight than metformin + SU + DPP4i, metformin + SU + insulin and metformin + SU + TZDs; metformin + SU + DPP4i resulted in significantly lower body
metformin 24494 resulted in significantly lower body weight than metformin + SU + DPP4i, metformin + SU + insulin and metformin + SU + TZDs; metformin + SU + DPP4i resulted in significantly lower body weight than metformin + SU
metformin 24517 lower body weight than metformin + SU + DPP4i, metformin + SU + insulin and metformin + SU + TZDs; metformin + SU + DPP4i resulted in significantly lower body weight than metformin + SU + insulin and metformin
metformin 24589 and metformin + SU + TZDs; metformin + SU + DPP4i resulted in significantly lower body weight than metformin + SU + insulin and metformin + SU + TZD.Metformin + SU + insulin, metformin + SU + TZD and metformin
metformin 24618 metformin + SU + DPP4i resulted in significantly lower body weight than metformin + SU + insulin and metformin + SU + TZD.Metformin + SU + insulin, metformin + SU + TZD and metformin + SU + DPP4i increased the odds
metformin 24665 lower body weight than metformin + SU + insulin and metformin + SU + TZD.Metformin + SU + insulin, metformin + SU + TZD and metformin + SU + DPP4i increased the odds of hypoglycaemia when compared to metformin
metformin 24690 metformin + SU + insulin and metformin + SU + TZD.Metformin + SU + insulin, metformin + SU + TZD and metformin + SU + DPP4i increased the odds of hypoglycaemia when compared to metformin + SU. Metformin + SU + GLP-1RA
metformin 24766 metformin + SU + TZD and metformin + SU + DPP4i increased the odds of hypoglycaemia when compared to metformin + SU. Metformin + SU + GLP-1RA reduced the odds of hypoglycemia compared to metformin + SU + insulin.Lee
metformin 24852 when compared to metformin + SU. Metformin + SU + GLP-1RA reduced the odds of hypoglycemia compared to metformin + SU + insulin.Lee et al. (2016) [[42]]40 RCTS comparing dual therapy to any triple combinations (15,182
metformin 25619 (5.94).Lozano-Ortega et al. (2016) [[43]]30 RCTs comparing SGLT2i to other drugs as add-on therapy to metformin and SUThe mean change (%) in HbA1c levels compared to placebo was –0.86 for SGLT2i, –0.68 for DPP4i,
pioglitazone 13068 than in Caucasians. In the study comparing the efficacy of vildagliptin (50 mg twice daily) to that of pioglitazone (15 mg once daily) as an add-on treatment to metformin in Korean patients with T2DM, the efficacy of
pioglitazone 13248 patients with T2DM, the efficacy of vildagliptin to lower the HbA1c level was not inferior to that of pioglitazone , and vildagliptin had beneficial effects on postprandial glucose levels compared to pioglitazone [[35]].
pioglitazone 13345 of pioglitazone, and vildagliptin had beneficial effects on postprandial glucose levels compared to pioglitazone [[35]]. On the other hand, in the study comparing the efficacy of lobeglitazone and pioglitazone as
pioglitazone 13442 to pioglitazone [[35]]. On the other hand, in the study comparing the efficacy of lobeglitazone and pioglitazone as add-ons to metformin, both of them decreased HbA1c by 0.74% at week 24 [[36]]. Therefore, the efficacy
pioglitazone 13721 in Koreans.In the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive Study), pioglitazone reduced the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients
pioglitazone 14015 a cohort study of 349,476 patients with T2DM, using the Korean NHIS claims database, treatment with pioglitazone + metformin was associated with decreased total CVD (HR, 0.89; 95% CI, 0.81 to 0.99), ischemic stroke
pioglitazone 23545 placebo/control.SGLT2i, rosiglitazone and liraglutide decreased SBP compared with placebo/ control, pioglitazone , glargine and sitagliptin (2.41–8.88 mmHg)Glargine, TZDs, liraglutide, sitagliptin, and canagliflozin
rosiglitazone 14660 long-term glycemic control in T2DM, the cumulative incidence of monotherapy failure at 5 years was 15% with rosiglitazone , 21% with metformin, and 34% with glyburide [[38]]. Therefore, it is difficult to say that either DPP4i
rosiglitazone 23469 glargine and sitagliptin caused weight gain (1.48–3.62 kg) compared with placebo/control.SGLT2i, rosiglitazone and liraglutide decreased SBP compared with placebo/ control, pioglitazone, glargine and sitagliptin
rosiglitazone 23769 increased hypoglycemia risk compared with placebo/control (relative risk, 1.92–7.47), while glargine and rosiglitazone increased hypoglycemia compared with most antihyperglycemic agents (relative risk, 2.81–7.47).Canagliflozin
sitagliptin 23383 acarbose to 1.20% for liraglutide)SGLT2i reduced weight (1.43–2.07 kg), whereas TZDs, glargine and sitagliptin caused weight gain (1.48–3.62 kg) compared with placebo/control.SGLT2i, rosiglitazone and liraglutide
sitagliptin 23572 rosiglitazone and liraglutide decreased SBP compared with placebo/ control, pioglitazone, glargine and sitagliptin (2.41–8.88 mmHg)Glargine, TZDs, liraglutide, sitagliptin, and canagliflozin increased hypoglycemia
sitagliptin 23631 placebo/ control, pioglitazone, glargine and sitagliptin (2.41–8.88 mmHg)Glargine, TZDs, liraglutide, sitagliptin , and canagliflozin increased hypoglycemia risk compared with placebo/control (relative risk, 1.92–7.47),
Select Disease Character Offset Disease Term Instance
diabetes mellitus 118 Journal of Internal MedicineCombination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus Min Kyong MoonKyu Yeon HurSeung-Hyun KoSeok-O ParkByung-Wan LeeJin Hwa KimSang Youl RheeHyun Jin KimKyung
diabetes mellitus 563 the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not
diabetes mellitus 2908 position statement regarding pharmacological therapies for non-pregnant adult patients with type 2 diabetes mellitus (T2DM), extensive review of scientific evidence, including the results of clinical trials of OHAs for
diabetes mellitus 20944 with significant weight loss (2.2 kg) compared to SU.RCT, randomized controlled trial; T2DM, type 2 diabetes mellitus ; DPP4i, dipeptidyl peptidase-4 inhibitor; SU, sulfonylurea; MD, mean difference; CI, confidence interval;
diabetes mellitus 26067 showed either an increase or no changes in weight or SBP.RCT, randomized controlled trial; T2DM, type 2 diabetes mellitus ; SU, sulfonylurea; HbA1c, glycosylated hemoglobin; SGLT2i, sodium-glucose cotransporter-2 inhibitor;
diabetic ketoacidosis 11154 deciding which drug is better. First, adverse reactions of SGLT2i such as urogenital infection, euglycemic diabetic ketoacidosis , or dehydration may limit the use of SGLT2i. Second, DPP4i have been reported to be more effective in
hypoglycemia 1129 added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent
hypoglycemia 1410 the patient’s clinical characteristics and the efficacy, side effects, mechanism of action, risk of hypoglycemia , effect on body weight, patient preference, and combined comorbidity. In this review, we address the
hypoglycemia 4201 a class of antihyperglycemic agents for combination therapy, the glucose-lowering efficacy, risk of hypoglycemia , body weight gain, and cardiovascular benefits associated with the drugs are preferentially considered
hypoglycemia 6081 significant difference at 52 and 104 weeks [[7]]. As we expected, DPP4i was associated with a lower risk of hypoglycemia (odds ratio [OR], 0.12) and weight gain (–0.58 kg) compared to SU. In terms of cardiovascular (CV)
hypoglycemia 7638 (0.15%) than SU did (Table 2) [[6],[13]-[16]]. In addition, SGLT2i was associated with a lower risk of hypoglycemia and less body weight gain [[6],[8],[13]]. Because these analyses included only three studies, and differences
hypoglycemia 9512 to 1.76) than with SU [[8]]. In addition, both DPP4i and SGLT2i were associated with a lower risk of hypoglycemia compared to SU, and the ORs of both drugs were similar to 0.12 [[19]].The CV safety of DPP4i has been
hypoglycemia 16194 and the TZDs and DPP4i resulted in significant weight gain compared with placebo/control. In terms of hypoglycemia , although the results are different among the analyses, TZDs as add-on therapy to metformin + SU were
hypoglycemia 16355 analyses, TZDs as add-on therapy to metformin + SU were associated with significantly higher rates of hypoglycemia [[8],[44]]. It seems there are no statistically significant differences in the risks of hypoglycemia
hypoglycemia 16456 hypoglycemia [[8],[44]]. It seems there are no statistically significant differences in the risks of hypoglycemia among most triple therapies [[41]]. In terms of CV safety, there was no evidence of significantly different
hypoglycemia 16850 combination of metformin + SU + TZD is the best in lowering HbA1c, but it is the worst in weight gain and hypoglycemia . The combination of metformin + SU + SGLT2i is the second-best in lowering HbA1c, but it is the best
hypoglycemia 18784 characteristics, with the goal of reducing blood glucose levels and side effects, including weight gain and hypoglycemia .Table 1.Summary of meta-analyses reviewed for comparison of sulfonylurea and DPP-4 inhibitor as an add-on
hypoglycemia 19756 respectively)SU was associated with weight gain and DPP4i with weight loss at all time-points.The incidence of hypoglycemia at 12, 52, and 104 weeks was significantly greater with SU (20%, 24%, and 27% respectively) compared
hypoglycemia 20530 CI, –0.701 to 0.869; p = 0.833).DPP4i had a favorable insulin resistance and low risk for AE and hypoglycemia .Foroutan et al. (2016) [[10]]10 RCTs comparing DPP4i to SU as add-on therapy to metformin (10,139 subjects)DPP4i
hypoglycemia 23672 sitagliptin (2.41–8.88 mmHg)Glargine, TZDs, liraglutide, sitagliptin, and canagliflozin increased hypoglycemia risk compared with placebo/control (relative risk, 1.92–7.47), while glargine and rosiglitazone increased
hypoglycemia 23793 compared with placebo/control (relative risk, 1.92–7.47), while glargine and rosiglitazone increased hypoglycemia compared with most antihyperglycemic agents (relative risk, 2.81–7.47).Canagliflozin increased the
hypoglycemia 24827 odds of hypoglycaemia when compared to metformin + SU. Metformin + SU + GLP-1RA reduced the odds of hypoglycemia compared to metformin + SU + insulin.Lee et al. (2016) [[42]]40 RCTS comparing dual therapy to any triple
hypoglycemia 25419 with none/placebo added to dual therapy.Compared with none/placebo added to dual therapy, the odds of hypoglycemia were higher for DPP4i (1.95), SGLT2i (2.27), GLP-1RA (2.61), TZD (2.83), and insulin (5.94).Lozano-Ortega
type 2 diabetes mellitus 111 Korean Journal of Internal MedicineCombination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus Min Kyong MoonKyu Yeon HurSeung-Hyun KoSeok-O ParkByung-Wan LeeJin Hwa KimSang Youl RheeHyun Jin KimKyung
type 2 diabetes mellitus 556 updated the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not
type 2 diabetes mellitus 2901 this 2017 position statement regarding pharmacological therapies for non-pregnant adult patients with type 2 diabetes mellitus (T2DM), extensive review of scientific evidence, including the results of clinical trials of OHAs for
type 2 diabetes mellitus 20937 associated with significant weight loss (2.2 kg) compared to SU.RCT, randomized controlled trial; T2DM, type 2 diabetes mellitus ; DPP4i, dipeptidyl peptidase-4 inhibitor; SU, sulfonylurea; MD, mean difference; CI, confidence interval;
type 2 diabetes mellitus 26060 treatments showed either an increase or no changes in weight or SBP.RCT, randomized controlled trial; T2DM, type 2 diabetes mellitus ; SU, sulfonylurea; HbA1c, glycosylated hemoglobin; SGLT2i, sodium-glucose cotransporter-2 inhibitor;

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