Linagliptin as add-on therapy to insulin for patients with type 2 diabetes

Figures & data

Table 2 Selected efficacy data from clinical trials of linagliptin as add-on to insulin and other antidiabetic therapies

Study	Duration	Patients	Background therapy	Intervention	Baseline HbA1c, mean (%)	Δ from placebo, HbA1c(%)	Δ from placebo, FPG (mmol/L)
McGill et al^Citation1	52	133;eGFR	• Insulin ± any combination <30 mL/min/1.73 m^2 • Glinides • Pioglitazone • Any other antidiabetics, excluding any other DPP-4 inhibitor	5 mg linagliptin orally once daily • Sulfonylurea	>7 and ≤10	−0.60* at week 12 −0.72* at week 51	−0.10; P=0.8802 at week 24 0.07; P=0.8698 at week 52
Yki-Järvinen et al^Citation3	52	1,261	• Basal insulin ± metformin ± pioglitazone	5 mg linagliptin orally once daily	8.29 (placebo) 8.31 (linagliptin)	−0.65* at week 24 −0.53* at week 52	−0.6;P<0.001 at week 24 No difference at week 52
Barnett et al^Citation2	24	241; age ≥70 years	• Metformin ± sulfonylurea ± insulin	5 mg linagliptin orally once daily	≥7.0	−0.64*	−1.15*

Note:

* P<0.0001.

Abbreviations: DPP, dipeptidyl peptidase; eGFR, estimated glomerular filtration rate; HbA_1c, glycated hemoglobin; FPG, fasting plasma glucose.

Table 1 Advantages and disadvantages of treatment with insulin and incretins

Advantages: insulin	Advantages: incretins	Advantages: combination insulin and linagliptin
Most effective blood glucose-lowering therapy^Citation39	Safe and effective improvement of glycemic control^Citation26	Reduction of hypoglycemia risk^Citation30,Citation31
Most clinical experience^Citation39	Blood sugar−dependent mode of action^Citation19,Citation20	Reduction of insulin-associated weight gain, by decreasing insulin dose^Citation25,Citation32
No maximum dose-effect threshold^Citation39	Counter-regulation of hypoglycemia^Citation30,Citation31
Beneficial effects on hypertriglyceridemia^Citation18	No weight gain^Citation25,Citation32 Primarily targets postprandial glycemia^Citation8 Oral administration^Citation26
Disadvantages: insulin	Disadvantages: incretins	Disadvantages: combination insulin and linagliptin
Blood sugar−independent mode of action^Citation15	Lack of long-term safety evaluations^Citation8	Lack of long-term safety evaluations^Citation8
Mode of administration^Citation39	Decline of insulin-releasing effect with progressive beta cell failure^Citation24
Associated with weight gain^Citation32
High risk for hypoglycemia^Citation29

Figure 1 Risk of overall hypoglycemia modified from Inzucchi et al.¹⁰⁰

Abbreviation: OAD, oral antidiabetic drug.

Figure 2 Mode of action of incretins according to glycemic state.

Notes: DPP-4 inhibition leads to an extension of physiological increases in GLP-1 and GIP, which also affects the fasting plasma levels of these incretins. However, there is accumulating evidence that GLP-1 and GIP have different modes of action according to the glycemic state.
Abbreviations: DPP, dipeptidyl peptidase; GIP, glucose-dependent insulinotropic polypeptide; GLP, glucagon-like peptide.

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