PMID- 23322141
OWN - NLM
STAT- MEDLINE
DCOM- 20130405
LR  - 20130116
IS  - 1941-9260 (Electronic)
IS  - 0032-5481 (Linking)
VI  - 124
IP  - 6
DP  - 2012 Nov
TI  - Evolving therapeutic options for type 2 diabetes mellitus: an overview.
PG  - 82-9
LID - 10.3810/pgm.2012.11.2614 [doi]
AB  - INTRODUCTION: Many oral antidiabetic drugs (OADs) are available for patients with 
      type 2 diabetes mellitus (T2DM). However, it is recognized that additional 
      therapies are needed and several new compounds are in advanced stages of 
      development. PURPOSE: This narrative review considers the essential features of a 
      successful OAD, the main classes of OADs that are currently used, and the 
      therapies that may be available in the upcoming years. RESULTS AND CONCLUSIONS: 
      The first OADs (sulfonylureas and biguanides) were discovered by chance. Although 
      effective in reducing blood glucose levels, early sulfonylureas were associated 
      with significant off-target effects, and the biguanide phenformin was 
      discontinued due to adverse events. Although metformin is in the same drug class, 
      it has a better safety profile and is now recommended as first-line treatment, 
      except when contraindicated. Nonetheless, many patients require additional 
      glucose control (even on metformin) with an agent that has a complementary 
      mechanism of action. Developments in bench science have facilitated the selection 
      of agents for specific therapeutic targets, with the thiazolidinediones providing 
      an interesting example. This OAD class initially appeared encouraging, yet in 
      clinical practice was associated with safety concerns. As a result, newer agents, 
      such as dipeptidyl peptidase-4 inhibitors, are undergoing more rigorous safety 
      evaluations than OADs of previous generations. Promising compounds with novel 
      mechanisms of action include the sodium-glucose co-transporter 2 inhibitors, the 
      G-protein-coupled receptor agonists, and the balanced dual peroxisome 
      proliferator-activated receptor-alpha/gamma agonists. There is optimism that in the next 
      few years, novel classes of OADs that are currently under development will offer 
      additional blood glucose control options via complementary mechanisms of action. 
      However, history has shown that compounds of the same class can have different 
      safety profiles and treatment effects. Therefore, high-quality clinical trial 
      evidence is needed for every compound.
FAU - Guthrie, Robert M
AU  - Guthrie RM
AD  - Emergency Medicine, Ohio State University, 6408 Phoenix Park Dr., Dublin, OH 
      43016, USA. robertguthriemd@gmail.com
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Postgrad Med
JT  - Postgraduate medicine
JID - 0401147
RN  - 0 (Biguanides)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sulfonylurea Compounds)
RN  - 0 (Thiazolidinediones)
SB  - IM
MH  - Biguanides/therapeutic use
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Sulfonylurea Compounds/therapeutic use
MH  - Thiazolidinediones/therapeutic use
EDAT- 2013/01/17 06:00
MHDA- 2013/04/06 06:00
CRDT- 2013/01/17 06:00
PHST- 2013/01/17 06:00 [entrez]
PHST- 2013/01/17 06:00 [pubmed]
PHST- 2013/04/06 06:00 [medline]
AID - 10.3810/pgm.2012.11.2614 [doi]
PST - ppublish
SO  - Postgrad Med. 2012 Nov;124(6):82-9. doi: 10.3810/pgm.2012.11.2614.