DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

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Term Occurence Count Dictionary
diabetes mellitus 4 endocrinologydiseases
hyperglycemia 3 endocrinologydiseases
hypoglycemia 13 endocrinologydiseases
metformin 2 endocrinologydiseasesdrugs
sitagliptin 21 endocrinologydiseasesdrugs
type 1 diabetes mellitus 1 endocrinologydiseases
Insulin 5 endocrinologydiseasesdrugs
lansoprazole 4 endocrinologydiseasesdrugs
type 2 diabetes mellitus 1 endocrinologydiseases
diabetic retinopathy 1 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
Insulin 2067 with an annual increase of 3.8–5.6% [[2]–[4]], but this proportion may be underestimated [[5]]. Insulin replacement has been the mainstay of therapy for T1DM [[6]]. New therapies, including immunotherapy,
Insulin 7028 levels, as well as the area under the curve (AUC) for the blood glucose levels during a specific period). Insulin dosage, cholesterol, triglycerides, and adverse events were classified as secondary outcomes. We extracted
Insulin 10603 insulin compared with insulin monotherapy on T1DM, and the other study [[13]] investigated vildagliptin. Insulin injections were described in detail for both the experimental and control groups. Twelve patients from
Insulin 30738 (unspecified)Vildagliptin (50 mg, bid) + insulinc (long-acting and short-acting insulin)Control treatmentd Insulin (bid-tid)Placebo + insulinPlacebo + insulinInsulinPlacebo + insulinTreatment period (weeks)525216528Experimental
Insulin 30797 and short-acting insulin)Control treatmentdInsulin (bid-tid)Placebo + insulinPlacebo + insulin Insulin Placebo + insulinTreatment period (weeks)525216528Experimental samples640631514Control samples618621514Average
lansoprazole 11717 placebo-controlled clinical trial from the United States [[8]] aimed to test the efficacy of the combination of lansoprazole with sitagliptin on T1DM. A randomized, double-blind, placebo-controlled trial with the largest sample
lansoprazole 14247 declined significantly in the groups that received one year of combination therapy with sitagliptin and lansoprazole or the placebo control, but the difference between the treatment groups was insignificant. In contrast,
lansoprazole 18035 glucose levels increased by 2.04 mmol/L (95% CI: 1.09–2.99) in the group receiving sitagliptin and lansoprazole combined with insulin and by 3.05 mmol/L (95% CI: 1.17–4.92) in the insulin monotherapy group, but
lansoprazole 30459 treatmentSitagliptin (100 mg, qd) + insulina (premix insulin)Sitagliptin (100/50 mg, qd) + lansoprazole (60/30 mg, qd) + insulin (unspecified)Sitagliptin (100 mg, qd) + insulinb (premixed insulin
metformin 26616 compared to glimepiride administration for 104 weeks as an add-on therapy to preferably >1500 mg of metformin in patients with T2DM with insufficient glycemic control. Some of the participants were reclassified
metformin 26955 demonstrated progressively increasing C-peptide levels and slightly decreasing HbA1c levels after linagliptin- metformin treatment compared to the baseline levels [[38]], hinting at a possible therapeutic effect of DPP-4
sitagliptin 5304 inhibitors” OR “dpp-4 inhibitor” OR dutogliptin OR alogliptin OR linagliptin OR saxagliptin OR sitagliptin OR vildagliptin) AND (“type 1 diabetes” OR t1dm). Publications were searched in Medline and Embase
sitagliptin 10482 medicine options, four studies [[8], [18]–[20]] examined the effects of combination therapy comprising sitagliptin and insulin compared with insulin monotherapy on T1DM, and the other study [[13]] investigated vildagliptin.
sitagliptin 11095 studies, one study [[18]] was conducted on LADA patients. This study was designed to determine whether sitagliptin protected islet β-cells in patients with LADA. Regarding indicators, the earliest initiated study was
sitagliptin 11507 glycemia after DPP-4 inhibitor treatment of patients with new-onset T1DM to explore the advantages of a sitagliptin and insulin combination compared with insulin monotherapy. A multicenter, randomized, placebo-controlled
sitagliptin 11735 trial from the United States [[8]] aimed to test the efficacy of the combination of lansoprazole with sitagliptin on T1DM. A randomized, double-blind, placebo-controlled trial with the largest sample size (125 subjects)
sitagliptin 11922 largest sample size (125 subjects) conducted in the United States [[20]] aimed to explore the effect of sitagliptin on the postprandial glucagon and GLP-1 levels. Table 1 shows the characteristics of the included studies.
sitagliptin 12851 C-peptide level remain controversial. One study [[18]] reported a positive effect and concluded that sitagliptin at least attenuated the progressive decrease in the C-peptide levels. Three studies [[8], [19], [20]]
sitagliptin 13326 (2 h CP) level ≥ 400 pmol/L. After 1 year of treatment, the participants who were administered sitagliptin and insulin had no evident decrease in their fasting C-peptide levels, 2-hour postprandial C-peptide
sitagliptin 13847 C-peptide was elevated by 0.0067 ± 0.19 ng/mL or −0.05 ± 0.28 ng/mL in the groups treated with sitagliptin alone or the combination of sitagliptin and insulin, respectively. However, neither the changes in the
sitagliptin 13887 0.19 ng/mL or −0.05 ± 0.28 ng/mL in the groups treated with sitagliptin alone or the combination of sitagliptin and insulin, respectively. However, neither the changes in the C-peptide levels in the groups nor between
sitagliptin 14231 and 12 months declined significantly in the groups that received one year of combination therapy with sitagliptin and lansoprazole or the placebo control, but the difference between the treatment groups was insignificant.
sitagliptin 14650 study by Garg et al. [[20]], and the C-peptide-positive patients who were randomly allocated to receive sitagliptin had a nonsignificant trend toward decreased HbA1c levels, mean glucose levels, and duration of hyperglycemia.
sitagliptin 15766 RCTs did not observe a significant improvement in the HbA1c levels when the patients were treated with sitagliptin [[19], [20]] or vildagliptin [[13]] in addition to insulin therapy. The authors in the other RCT [[18]]
sitagliptin 16074 showed an advantage for the HbA1c levels in the group that received combination treatment including sitagliptin over insulin monotherapy. Overall, a meta-analysis of these four studies (shown in Figure 3(a)) suggested
sitagliptin 16867 different medicines (vildagliptin was used in Farngren et al.'s study, while the other studies used sitagliptin ). Then, we performed a subgroup analysis. The vildagliptin subgroup showed advantages over insulin monotherapy
sitagliptin 17142 −0.38%–0.26%)) in the study by Farngren et al. [[13]]. However, the subgroup of the other three studies on sitagliptin suggested that it was no better than insulin monotherapy. As shown in Figure 3(b), the change in the
sitagliptin 18019 2-hour blood glucose levels increased by 2.04 mmol/L (95% CI: 1.09–2.99) in the group receiving sitagliptin and lansoprazole combined with insulin and by 3.05 mmol/L (95% CI: 1.17–4.92) in the insulin monotherapy
sitagliptin 18681 by Hari et al. [[19]] revealed a significantly greater decrease in daily insulin consumption in the sitagliptin group (23.7 ± 13.9 U) than in the control group (15.2 ± 9.5 U) at the end of one year.
sitagliptin 19595 over time.According to Garg et al. [[20]], the GLP-1 levels measured after 30 and 60 minutes in the sitagliptin group were significantly elevated after 16 weeks of treatment, whereas the GIP level measured at the
sitagliptin 20256 cholesterol, triglycerides, and total cholesterol) between the treatment groups after treatment with sitagliptin for 12 months. In the study by Hari et al. [[19]], the BMI was significantly increased (1.5 ± 2.15 kg/m2,
sitagliptin 20942 [[19]] observed a high incidence of hypoglycemia, including severe hypoglycemia (4/6 versus 3/6 in the sitagliptin group compared with the insulin monotherapy group). Griffin et al. [[8]] reported adverse events of
Select Disease Character Offset Disease Term Instance
diabetes mellitus 530 have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic
diabetes mellitus 1692 positive effects in clinical practice. Further optimized clinical trials are needed.1. IntroductionType 1 diabetes mellitus (T1DM) is considered a chronic immune-mediated disease that is characterized by the selective destruction
diabetes mellitus 1886 by the selective destruction of β-cells in genetically susceptible individuals. The proportion of diabetes mellitus patients diagnosed with T1DM is estimated to be 5%–10% [[1]] with an annual increase of 3.8–5.6%
diabetes mellitus 2990 been widely used as outstanding blood glucose-dependent antidiabetic agents for patients with type 2 diabetes mellitus (T2DM), show promise. These inhibitors prevent the degradation of incretin (glucagon-like peptide-1
diabetic retinopathy 25195 cases [[32]]. Moreover, DPP-4 inhibition increased the survival of islet grafts [[33]] and improved diabetic retinopathy [[34]]. According to clinical studies, patients with T1DM displayed higher DPP-4 levels [[35], [36]].
hyperglycemia 3969 patients with T1DM [[11]], increased [[10]]. Glucagon levels have been shown to be decreased during hyperglycemia [[12]–[15]] in several clinical trials of T1DM. However, controlled clinical trials have reported
hyperglycemia 14757 sitagliptin had a nonsignificant trend toward decreased HbA1c levels, mean glucose levels, and duration of hyperglycemia . The data were not available for the C-peptide-negative patients. All 28 participants with T1DM enrolled
hyperglycemia 28260 significantly increased the GLP-1 and GIP levels [[13], [14], [40]], reduced the glucagon levels during hyperglycemia , and sustained glucagon counterregulation during hypoglycemia in patients with T1DM [[13], [14]]. Fortunately,
hypoglycemia 20690 the body weight or BMI between groups.(2) Overall Adverse Events and Side Effects. We believe that hypoglycemia is one vital adverse event that deserves more attention when antidiabetic agents are added to insulin
hypoglycemia 20875 antidiabetic agents are added to insulin therapy. The study by Hari et al. [[19]] observed a high incidence of hypoglycemia , including severe hypoglycemia (4/6 versus 3/6 in the sitagliptin group compared with the insulin monotherapy
hypoglycemia 20906 therapy. The study by Hari et al. [[19]] observed a high incidence of hypoglycemia, including severe hypoglycemia (4/6 versus 3/6 in the sitagliptin group compared with the insulin monotherapy group). Griffin et al.
hypoglycemia 21061 compared with the insulin monotherapy group). Griffin et al. [[8]] reported adverse events of severe hypoglycemia (<2.06 mmol/L) in 11 (24%) and 7 (32%) of the patients in the experimental and control groups, respectively.
hypoglycemia 21199 (24%) and 7 (32%) of the patients in the experimental and control groups, respectively. Additionally, hypoglycemia (<3.33 mmol/L) occurred in 44 (96%) and 19 (86%) patients in these two groups, respectively. Only
hypoglycemia 21364 patients in these two groups, respectively. Only one patient in the control group experienced severe hypoglycemia and required an insulin dosage adjustment after a period of 16 weeks in Garg et al.'s study [[20]].
hypoglycemia 21532 period of 16 weeks in Garg et al.'s study [[20]]. In the study by Zhao et al. [[18]], a low incidence of hypoglycemia (<3.9 mmol/L) occurred, and no severe hypoglycemia was reported. Finally, none of these studies observed
hypoglycemia 21585 study by Zhao et al. [[18]], a low incidence of hypoglycemia (<3.9 mmol/L) occurred, and no severe hypoglycemia was reported. Finally, none of these studies observed a significant difference in the incidence of hypoglycemia.
hypoglycemia 21697 was reported. Finally, none of these studies observed a significant difference in the incidence of hypoglycemia . We tried to obtain information regarding the time spent in hypoglycemia, but the studies included in
hypoglycemia 21770 difference in the incidence of hypoglycemia. We tried to obtain information regarding the time spent in hypoglycemia , but the studies included in the present meta-analysis did not report this information. In another study
hypoglycemia 21896 studies included in the present meta-analysis did not report this information. In another study [[13]], hypoglycemia was designed to be induced by a hyperinsulinemic hypoglycemic clamp and therefore was not valued as
hypoglycemia 23327 that no serious side effects were confirmed to be clearly related to the DPP-4 inhibitors, including hypoglycemia , and other causes led to discontinuation from further participation; in addition, ketoacidosis and pancreatitis
hypoglycemia 28323 [40]], reduced the glucagon levels during hyperglycemia, and sustained glucagon counterregulation during hypoglycemia in patients with T1DM [[13], [14]]. Fortunately, the absence of relevant severe side effects promises
type 1 diabetes mellitus 523 studies have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic
type 2 diabetes mellitus 2983 have been widely used as outstanding blood glucose-dependent antidiabetic agents for patients with type 2 diabetes mellitus (T2DM), show promise. These inhibitors prevent the degradation of incretin (glucagon-like peptide-1

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