PMID- 23680741
OWN - NLM
STAT- MEDLINE
DCOM- 20130724
LR  - 20181202
IS  - 2154-8331 (Print)
IS  - 2154-8331 (Linking)
VI  - 41
IP  - 2
DP  - 2013 Apr
TI  - Combination therapy with DPP-4 inhibitors and insulin in patients with type 2 
      diabetes mellitus: what is the evidence?
PG  - 93-107
LID - 10.3810/hp.2013.04.1059 [doi]
AB  - As type 2 diabetes mellitus (T2DM) progresses, most patients will require insulin 
      replacement therapy. Whether oral antidiabetic drug (OAD) therapy should be 
      retained when initiating insulin is still debated. While the rationale to keep 
      metformin with insulin is strong (mostly as an insulin-sparing agent to limit 
      weight gain), the evidence is less clear for other OADs. In particular, the 
      question now comes up what the expected benefit could be of combining the newer 
      agents, such as the dipeptidyl peptidase-4 (DPP-4) inhibitors with insulin. 
      Additionally, when metformin is no longer a treatment option, as in the case of 
      patients with severe renal impairment, insulin is often used as monotherapy, with 
      little evidence of benefit in maintaining other OADs. In this specific situation, 
      it is also of interest to evaluate the potential benefit of combined treatment 
      with a DPP-4 inhibitor and insulin. Among the classic limitations of insulin 
      therapy in patients with T2DM, hypoglycemia remains a major barrier to glycemic 
      control, along with weight gain exacerbation. The oral DPP-4 inhibitors improve 
      glycemic control by increasing the sensitivity of the islet cells to glucose, and 
      thus are not associated with an increased risk for hypoglycemia and are weight 
      neutral. In addition to the expected benefits associated with limiting insulin 
      dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug 
      class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors 
      with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease 
      glycemic excursions that are not properly addressed by basal insulin therapy and 
      metformin use, even after optimizing titration of the basal insulin. However, 
      given the common original perception that treatment with DPP-4 inhibitors may be 
      less beneficial with increasing disease progression because of the loss of beta-cell 
      function, the potential relevance of these agents in the setting of advanced T2DM 
      treated with insulin was not necessarily anticipated. Promising data from studies 
      on the use of these new agents in insulin-treated patients with T2DM have started 
      to emerge. Our article provides a comprehensive overview of the currently 
      available evidence from controlled randomized clinical trials and we discuss the 
      potential role of DPP-4 inhibitors in the this setting. Further clinical 
      experience will allow to fully assess the positioning of these agents in 
      insulin-treated T2DM populations.
FAU - Charbonnel, Bernard
AU  - Charbonnel B
AD  - Department of Endocrinology, University of Nantes, Hopital Laennec, Nantes, 
      France.
FAU - Schweizer, Anja
AU  - Schweizer A
FAU - Dejager, Sylvie
AU  - Dejager S
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Hosp Pract (1995)
JT  - Hospital practice (1995)
JID - 101268948
RN  - 0 (Dipeptides)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Nitriles)
RN  - 0 (Piperidines)
RN  - 0 (Purines)
RN  - 0 (Pyrazines)
RN  - 0 (Pyrrolidines)
RN  - 0 (Quinazolines)
RN  - 0 (Triazoles)
RN  - 3X29ZEJ4R2 (Linagliptin)
RN  - 56HH86ZVCT (Uracil)
RN  - 9GB927LAJW (saxagliptin)
RN  - I6B4B2U96P (Vildagliptin)
RN  - JHC049LO86 (alogliptin)
RN  - PJY633525U (Adamantane)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Adamantane/analogs & derivatives
MH  - Body Weight/drug effects
MH  - Diabetes Complications
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dipeptides
MH  - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage
MH  - Disease Progression
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Hypoglycemia/prevention & control
MH  - Hypoglycemic Agents/*administration & dosage
MH  - Insulin/*administration & dosage
MH  - Linagliptin
MH  - Nitriles
MH  - Piperidines
MH  - Purines
MH  - Pyrazines
MH  - Pyrrolidines
MH  - Quinazolines
MH  - Renal Insufficiency, Chronic
MH  - Sitagliptin Phosphate
MH  - Triazoles
MH  - Uracil/analogs & derivatives
MH  - Vildagliptin
EDAT- 2013/05/18 06:00
MHDA- 2013/07/25 06:00
CRDT- 2013/05/18 06:00
PHST- 2013/05/18 06:00 [entrez]
PHST- 2013/05/18 06:00 [pubmed]
PHST- 2013/07/25 06:00 [medline]
AID - 10.3810/hp.2013.04.1059 [doi]
PST - ppublish
SO  - Hosp Pract (1995). 2013 Apr;41(2):93-107. doi: 10.3810/hp.2013.04.1059.