Are there any studies/data that compare linagliptin with sitagliptin?

Are there any studies/data that compare linagliptin with sitagliptin?

Comment by InpharmD Researcher

Published literature comparing linagliptin with sitagliptin have reported conflicting degrees of efficacy, although one meta-analysis presents no differences between agents in clinical outcomes, such as achievement of HbA1c <7% and rate of hypoglycemia. Due to linagliptin’s non-renal pharmacokinetics, it may be a more attractive option over sitagliptin for patients with kidney dysfunction. Cost, availability, and patient choice are all factors that should be additionally considered in selection of an agent.

Background

A 2017 network meta-analysis was conducted to compare the efficacy of linagliptin and sitagliptin, two DDP-4 inhibitors, in treating patients with type 2 diabetes. From 32 included studies (N= 13,747 patients), the analysis found no significant difference between the two drugs in key outcomes such as HbA1c changes, body weight change, achievement of HbA1c <7, and hypoglycemic events. Linagliptin showed non-renal clearance, making it safer than sitagliptin for patients with kidney dysfunction. However, efficacy was the same between the drugs. When considering combinations with metformin, linagliptin was associated with greater weight loss compared to sitagliptin combinations. The authors concluded that linagliptin and sitagliptin have comparable efficacy. Due to linagliptin's renal safety profile, it may be preferable for patients with kidney issues, but choice depends on cost and availability. [1]

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

Are there any studies/data that compare linagliptin with sitagliptin?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Tables 1-3 for your response.

Comparison between the clinical efficacy of linagliptin and sitagliptin
Design	Prospective, comparative study N= 42
Objective	To compare the clinical efficacy of linagliptin with sitagliptin focusing on glycemic control, renal function, liver function, and lipid profile improvement in patients with type 2 diabetes
Study Groups	Linagliptin (n= 21) Sitagliptin (n= 21)
Inclusion Criteria	Patients with type 2 diabetes whose pharmacological treatment was recently initiated
Exclusion Criteria	N/A
Methods	Patients were randomly assigned to receive either sitagliptin 50 mg/day or linagliptin 5 mg/day.
Duration	24 hours after initiation
Outcome Measures	HbA1c levels, renal function (eGFR and creatinine), liver function (AST and ALT), and lipid profile (HDL-C and LDL-C)
Baseline Characteristics		Linagliptin (n= 21)	Sitagliptin (n= 21)
	Age, years	50.8	51.4
	Female	9	14
	HbA1c, mmol/mol	6.9	7.3
	Fasting blood glucose level, mg/dL	145.1	146.8
	HDL-C, mg/dL LDL-C, mg/dL	55.5 148.1	57.8 128.7
	Creatinine, mg/dL	0.65	0.57
	eGFR, mL/min/1.73m²	101.7	102.6
	AST, IU/L ALT, IU/L	29.8 42.8	34.2 45.5
Results	Endpoint	Linagliptin (n= 21)	Sitagliptin (n= 21)
	HbA1c, mmol/mol Difference p-Value	6.32 -0.62 < 0.05	6.72 -0.57 < 0.05
	HDL-C, mg/dL Difference LDL-C, mg/dL Difference	58.4 -2.9 106.24 41.9	59.0 -1.2 121.05 -7.7
	Creatinine, mg/dL Difference	0.64 -0.01	0.60 0.03
	eGFR, mL/min/1.73m2 Difference	102.0 -0.3	99.0 -3.6
	AST, IU/L Difference ALT, IU/L	23.3 -6.5 --	26.5 -7.7 --
Adverse Events	N/A
Study Author Conclusions	This study has demonstrated that linagliptin can be a valuable option in the treatment of patients with type 2 diabetes
InpharmD Researcher Critique	While the study suggests potential benefits of linagliptin, the sample size is small, and the study lacks a detailed account of adverse events. Further, large scale studies are required to confirm these findings.

References:
[1] Kamatani N, Katoh T, Sawai Y, Kanayama H, Katada N, Itoh M. Comparison between the clinical efficacy of linagliptin and sitagliptin. J Diabetes. 2013;4(4):51–54

Different effects of linagliptin and sitagliptin on blood pressure and renal function in Japanese patients with type 2 diabetes mellitus
Design	Open-label, observational pilot study N= 73
Objective	To compare and evaluate the effects of sitagliptin and linagliptin on systemic and renal hemodynamics in Japanese patients with type 2 diabetes mellitus
Study Groups	Sitagliptin (n= 73) Linagliptin (n= 73)
Inclusion Criteria	Type 2 diabetic outpatients treated with 50 mg/day of sitagliptin for at least one year without severe renal dysfunction
Exclusion Criteria	Severe renal dysfunction
Methods	Patients were switched from 50 mg/day of sitagliptin to 5 mg/day of linagliptin. Various parameters, including blood pressure, eGFR, and serum creatinine, were measured at the start and at 3-month intervals for one year. Retrospective data were also gathered from medical records for one year before switching.
Duration	The total duration of the study was two years; one year under sitagliptin followed by one year under linagliptin treatment
Outcome Measures	Primary: Changes in systolic and diastolic blood pressure, eGFR, and serum creatinine levels Secondary:
Baseline Characteristics		Study patients (N= 73)
	Age, years	66
	Female	32
	Duration of diabetes, years	15.3
	Body mass index (BMI), kg/m²	24.6
	HbA1c	7.3%
	Use of ACE-inhibitor (ACE-I) or angiotensin receptor blocker (ARB)	38%
	Use of calcium channel blocker (CCB)	32%
	Systolic blood pressure (SBP), mmHg Diastolic blood pressure (DBP), mmHg	128 68
	Serum creatinine concentration (sCR), mg/dL	0.83
	Estimated glomerular filtration rate (eGFR; mL/min/1.73 m²	71.8
	Serum uric acid concentration, mg/dL	5.3
	Serum Na concentration, mEq/L	139.2
	Serum K concentration, mEq/L	4.5
Results	Endpoint	At 6 months after switching	At 1 year after switching
	BMI, kg/m²	23.8 ± 5.7	24.6 ± 4.1
	HbA1c	7.44 ± 1.25^^	7.46 ± 1.02^^
	Systolic blood pressure, mmHg Diastolic blood pressure, mmHg	134 ± 15* 73 ± 10	134 ± 15*** 71 ± 12*
	Serum creatinine concentration, mg/dl	0.82 ± 0.32	0.84 ± 0.37
	eGFR, mL/min/1.73 m²	72.8 ± 23.9	72.3 ± 25.6
	Serum uric acid concentration, mg/dl	5.17 ± 1.04***	5.24 ± 1.10***
	Serum Na concentration, mEq/l	140.3 ± 2.6	140.1 ± 2.8
	Serum K concentration, mEq/l	4.54 ± 0.4	4.46 ± 0.4
	* p< 0.05, p< 0.01, * p< 0.001 versus the value at switching from sitagliptin to linagliptin # p< 0.05, ^p< 0.01, ^^p< 0.001 versus the value at the initiation of sitagliptin
Adverse Events	N/A
Study Author Conclusions	The administration of sitagliptin had an obvious effect on the systemic or renal hemodynamics in contrast to the fact that the administration of L had no effect on these parameters. It is thus important to use these agents with different excretion routes, properly taking the patients’ renal function into account
InpharmD Researcher Critique	The study’s crossover design strengthened its findings, but limitations included the small sample size, lack of randomization, and retrospective data collection for sitagliptin. The results may not widely apply beyond the specific patient population studied (i.e., Japanese patients with type 2 diabetes)

References:
[1] Tojikubo M, Tajiri Y. Different effects of linagliptin and sitagliptin on blood pressure and renal function in Japanese patients with type 2 diabetes mellitus. Diabetol Int. 2017;8(4):397-401. Published 2017 Apr 24. doi:10.1007/s13340-017-0320-4

Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent
Design	Prospective, randomized, open-label, parallel clinical study N= 535
Objective	To evaluate the efficacy and safety of the three dipeptidyl peptidase 4 (DPP-4) inhibitors (vildagliptin, sitagliptin, and linagliptin) as add-on therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on dual combination of insulin and metformin or acarbose
Study Groups	Vildagliptin (n= 178) Sitagliptin (n= 178) Linagliptin (n= 178)
Inclusion Criteria	Adult patients with T2DM; HbA1c levels >7.0%; current treatment with insulin at a stable dose of 20-80 U daily and a traditional oral hypoglycemic agent (OHA; metformin 750-1,000 mg daily or acarbose 100-300 mg daily) for at least 12 weeks before screening
Exclusion Criteria	Type 1 diabetes mellitus or diabetes secondary to other conditions; unstable or severe comorbidity; history of kidney disease or clinical diagnosis of renal insufficiency; thyroid-stimulating hormone beyond the normal range; acute metabolic diabetic complications
Methods	Patients were randomized 1:1:1 to receive vildagliptin 50 mg BID, sitagliptin 100 mg QD, or linagliptin 5 mg QD for 12 weeks. Eating and exercise habits were kept consistent during the study. Patients were followed up every 2 weeks outpatient and provided dose adjustments of insulin or analogs depending on the patient's blood glucose levels. The DPP-4 inhibitor was administered as an add-on therapy, and background OHAs were maintained throughout therapy.
Duration	12 weeks
Outcome Measures	Primary: change in HbA1c and the proportion of patients that reached the target HbA1c level (<7.0%) from baseline to week 12 Secondary: changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), insulin dose from baseline to endpoint (week 12)
Baseline Characteristics		Sitagliptin (n= 165)*	Linagliptin (n= 164)*
	Age, years	56.04 ± 13.80	54.66 ± 10.85
	Male	104 (63.0%)	104 (63.4%)
	Body mass index, kg/cm²	26.51 ± 4.29	26.82 ± 4.80
	HbA1c, %	9.22 ± 1.60	9.58 ± 1.80
	Insulin dose, units	36.02 ± 1.06	33.43 ± 1.23
	Background OHA Metformin Acarbose	93 (56.4%) 72 (43.6%)	90 (54.9%) 74 (45.1%)
	*Discontinuation occurred throughout the study, and was mainly due to loss to follow-up, adverse events (i.e., hypoglycemia), or other reasons. Data has been specifically depicted for sitagliptin versus linagliptin.
Results	Endpoint	Sitagliptin (n= 165)	Linagliptin (n= 164)	p-value
	HbA1c at Week 12, % Change in HbA1c, %	8.26 ± 1.10 -0.84 ± 0.08	8.56 ± 1.96 -0.81 ± 0.08	NS
	Patients who reached target HbA1c	52.73%	55.49%	--
	Mean FPG values, mmol/L At week 6 At week 12	7.22 ± 1.47 8.02 ± 4.48	6.95 ± 1.27 6.90 ± 1.55	-- < 0.05
	Mean PPG values, mmol/L At week 6 At week 12	9.80 ± 2.23 10.58 ± 2.64	9.16 ± 2.24 9.03 ± 2.53	< 0.05 < 0.05
	Change in insulin at week 12, units	-12.81 ± 1.13	-8.63 ± 0.93	0.013
	Adverse events Hypoglycemia Gastrointestinal adverse events Renal and hepatic toxicity Infections Chest discomfort	17 (10.30%) 19 (11.52%) 5 (3.30%) 8 (4.85%) 11 (6.70%)	13 (7.29%) 15 (9.15%) 2 (1.22%) 12 (7.32%) 11 (6.71%)	0.460 0.323 0.366 0.644 0.713
	NS= not significant Data has been specifically depicted for sitagliptin versus linagliptin.
Adverse Events	See results; no severe AEs were reported. All AEs reported during the study were mild.
Study Author Conclusions	Vildagliptin, sitagliptin, or linagliptin appear to be effective and safe as add-on treatment for T2DM patients inadequately controlled on dual combination of insulin and another OHA. This is the first study to evaluate the efficacy and safety of this treatment regimen in Chinese T2DM patients. The three DPP-4 inhibitors had similar efficacy in achieving glycemic control, but vildagliptin was much more efficacious in decreasing insulin requirement and achieving target HbA1c level. Therefore, we consider that vildagliptin or any of the other tested DPP-4 inhibitors could be added to combination therapy to reach the glycemic control in inadequately controlled patients.
InpharmD Researcher Critique	Use of sitagliptin or linagliptin as adjunct agents in a small Chinese sample population at a single institution limits applicability of findings to other ethnic populations.

References:
[1] Tang YZ, Wang G, Jiang ZH, et al. Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent. Diabetol Metab Syndr. 2015;7:91. Published 2015 Oct 19. doi:10.1186/s13098-015-0087-3