Skip to main content

Main menu

  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us

Clinical Medicine Journal

  • ClinMed Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About ClinMed
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

User menu

  • Log in

Search

  • Advanced search
RCP Journals
Home
  • Log in
  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us
Advanced

Clinical Medicine Journal

clinmedicine Logo
  • ClinMed Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About ClinMed
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

The incretin system in the management of type 2 diabetes mellitus

Jeffrey W Stephens
Download PDF
DOI: https://doi.org/10.7861/clinmedicine.10-5-491
Clin Med October 2010
Jeffrey W Stephens
Diabetes Research Group, Institute of Life Sciences, Swansea University; Department of Diabetes and Endocrinology, Morriston Hospital, ABM University Health Board, Swansea
Roles: Reader in diabetes and endocrinology and honorary consultant physician
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: J.W.Stephens@Swansea.ac.uk
  • Article
  • Figures & Data
  • Info & Metrics
Loading
Key Words
  • dipeptidyl peptidase-IV (DPP-IV)
  • exenatide
  • glucagon-like peptide-1 (GLP-1) analogues
  • glycaemic control
  • liraglutide
  • obesity
  • type 2 diabetes mellitus

Key Points

Glucagon-like peptide-1 (GLP-1) levels are low in patients with type 2 diabetes mellitus (T2DM)

GLP-1 administration improves insulin secretion, reduces glucagon secretion, promotes satiety and delays gastric emptying

GLP-1 mimetics are efficacious in the treatment of T2DM; currently available agents include exenatide and liraglutide

Inhibitors of enzyme dipeptidyl peptidase-IV are available as oral agents for the treatment of T2DM

Type 2 diabetes mellitus (T2DM) is a progressive disease characterised by a variable degree of β-cell dysfunction, insulin resistance and hyperglycaemia. Recently there has been enormous interest in developing pharmacological agents which modulate the incretin system. These therapeutic agents improve glycaemic control through multiple mechanisms similar to the endogenous incretin hormone glucagon-like peptide-1 (GLP-1).1–3

The incretin effect

The incretin effect is a phenomenon by which oral glucose ingestion elicits a much higher insulin secretory response than intravenous glucose.1,4 Following an oral glucose load, GLP-1 is secreted from the intestinal mucosa and augments the insulin response to hyperglycaemia. Plasma levels of GLP-1 increase six- to eightfold after a carbohydrate meal.5 The action of GLP-1 is therefore dependent on residual insulin secretory capacity. GLP-1 is released in response to nutrient ingestion from L-cells distributed throughout the intestine, but preferentially located in the distal gut.6 It is of interest that plasma levels of GLP-1 increase within minutes of food consumption, suggesting that a combination of endocrine and neural signals promotes early GLP-1 secretion before digested food passes through the gut to directly engage the L-cells.1

In addition to its insulinotropic effect, GLP-1 inhibits glucagon release,6 prolongs gastric emptying and leads to a decrease in body weight, all of which explain the ‘antidiabetic’ effect of this incretin hormone.7 Endogenous GLP-1 undergoes rapid inactivation by the enzyme dipeptidyl peptidase-IV (DPP-IV), resulting in a plasma half-life of 1–2 min. Therefore, the therapeutic potential of endogenous GLP-1 would be limited without attempts to prolong its duration of action.

The therapeutic potential of the incretin system in type 2 diabetes mellitus

There is a moderate degree of GLP-1 hyposecretion in subjects with T2DM. The typical phenotype of T2DM consists of a heterogeneous picture of diminished insulin secretion, excess glucagon secretion relative to the plasma glucose, and increased body weight with associated insulin resistance. Rodent and in vitro studies have shown an increase in β-cell mass following long-term administration of GLP-1. An improvement in β-cell function has been observed in humans, with increased insulin secretory capacity in response to GLP-1.8 Infusion of GLP-1 results in the suppression of glucagon secretion and normalisation of fasting plasma glucose.8 Importantly, GLP-1 administration does not impair the glucagon counter-regulatory response to hypoglycaemia since glucagon secretion is glucose-dependent.9 GLP-1 has a direct action on the hypothalamus to induce satiety10 and also delays gastric emptying.11 Both these factors induce a feeling of postprandial ‘fullness’.

The physiological effects of GLP-1 in improving β-cell function, reducing glucagon secretion and gastric emptying, inducing satiety and facilitating weight loss would be ideal in the therapy of a typical subject with T2DM.

Therapeutic strategies based on the incretin system

The main challenge in using GLP-1 to treat T2DM relates to its rapid metabolism by plasma DPP-IV. Initial interest in the use of GLP-1 based therapies for T2DM focused on DPP-IV resistant peptides that bound to the GLP-1 receptor (GLP-1 agonists) or substances inhibiting DPP-IV which would increase endogenous levels of GLP-1.12 This led first to the development of incretin mimetics and subsequently of DPP-IV inhibitors.

GLP-1 mimetics

Two GLP-1 mimetics (also known as GLP-1 receptor agonists) are currently available in clinical practice: exenatide and liraglutide. They are DPP-IV resistant analogues of human GLP-1 that improve glycaemic control through multiple mechanisms similar to the endogenous incretin hormone GLP-1.1,2 The efficacy of both these agents has been established in phase III clinical trials.

Exenatide

The first product licensed was exenatide, a synthetic analogue of a 39-amino acid peptide (exendin-4) originally found in the saliva of the lizard Heloderma suspectum. It is a functional, partly DPP-IV-resistant analogue of human GLP-1.13 Studies have examined the efficacy of adding exenatide to concurrent oral therapy (metformin,14 sulphonylureas,15a combination of both16 or thiazolidinediones17) in patients with suboptimal glycaemic control. The starting dose of exenatide is 5 μg twice daily for four weeks followed by 10 μg twice daily thereafter.

Exenatide was associated with a mean reduction in HbA1c of 0.8–1.0% during 30 weeks of treatment, with a weight loss of 1.5–3.0 kg.14–16 Patients continuing in an open-label extension lost as much as 4–5 kg after 80 weeks.18,19 Furthermore, in a 26-week comparator study against insulin-glargine20 there was a similar overall improvement in glycaemic control (−1.1% reduction in HbA1c) with the additional benefit of sustained weight reduction (−2.3 kg with exenatide, +1.8 kg with insulin glargine).

A more recent study21 compared exenatide with biphasic insulin aspart as additional therapy in patients already receiving metformin and a sulphonylurea over a 52-week period. The HbA1c reduction was similar (−1% reduction) but weight loss was observed in the exenatide treated participants (−2.5 kg with exenatide, +2.9 kg with biphasic insulin). Favourable reports have also been obtained with exenatide in the routine clinical setting.22

Liraglutide

Liraglutide is a long-acting GLP-1 analogue with 97% sequence homology to human GLP-1 but with structural modifications that result in reversible albumin binding, resistance to GLP-1 inactivation by DPP-IV, and prolonged duration of action.23 The starting dose of liraglutide is 0.6 mg once a day increased weekly to a maximum of 1.8 mg daily.

The results of phase III clinical studies (Liraglutide Effects and Action in Diabetes (LEAD)) demonstrate the efficacy of liraglutide in reducing HbA1c and also show beneficial effects on body weight. The LEAD programme comprised six randomised controlled, double-blind studies examining the effect of liraglutide directly against commonly used therapies in T2DM. As shown in Table 1, HbA1c reduction is typical and weight loss was observed in all the studies except LEAD-1.17,24–28

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 1.

Summary of changes in HbA1c, body weight and systolic blood pressure (BP) in the Liraglutide Effects and Action in Diabetes (LEAD) studies.

It is of interest that a recent placebo-controlled study in obese individuals without T2DM demonstrated a significant weight reduction associated with liraglutide at 20 weeks.29 The mean weight loss observed with liraglutide doses of 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg were −4.8 kg, −5.5 kg, −6.3 kg and −7.2 kg, respectively, compared with −2.8 kg with placebo. At present, liraglutide is not licensed for use as a weight reducing agent.

In the LEAD-6 study24 the efficacy of liraglutide was compared with exenatide as add-on therapy to metformin and/or sulphonylurea. There was greater improvement in glycaemic control with once daily liraglutide compared with twice a day exenatide (reduction in mean HbA1c, −1.12% with liraglutide, 0.7% with exenatide).

Adverse effects

Table 2 summarises the main adverse effects associated with GLP-1 mimetics. Essentially, these are gastrointestinal (GI) disturbances and risk of hypoglycaemia. The former include nausea, vomiting and diarrhoea. Typically, these adverse events, which are dose-dependent,17 are often mild and diminish within a few days or weeks on continued therapy. Patients should be counselled with regard to the GI adverse effects to prevent unnecessary discontinuation and improve compliance.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 2.

Summary of common adverse effects associated with incretin-based therapy.

The frequency of hypoglycaemia depends on the oral hypoglycaemic agents co-administered.22 Importantly, the incidence of minor hypoglycaemia with liraglutide was comparable (3%) with that on placebo and 17% lower than with sulphonylurea.25,27 Similarly, exenatide is also associated with an increased risk of hypoglycaemia when co-administered with a sulphonylurea.16,20 Patients should exercise increased vigilance with regard to this potential adverse effect, particularly when using a combination of liraglutide and a sulphonylurea.

DPP-IV inhibitors

An alternative approach to the use of GLP-1 mimetics is to inhibit the breakdown of endogenous GLP-1. DPP-IV inhibitors mimic many actions of the GLP-1 mimetics, including the stimulation of insulin, inhibition of glucagon secretion and preservation of β-cell mass.30 DPP-IV inhibitors are not typically associated with decreased gastric emptying or clinically significant weight loss.

Several DPP-IV inhibitors are in development and have the advantage of oral administration. Currently licensed available agents include sitagliptin, vildagliptin and saxagliptin. Clinical studies have shown that vildagliptin is associated with a −0.8% change in HbA1c when combined with metformin therapy.31 As a monotherapy, similar reductions in HbA1c are seen compared with metformin32 and rosiglitazone.33 Clinical studies with sitagliptin have shown a −0.65% change in HbA1c when combined with metformin therapy.34 Monotherapy at a dose of 100 mg/day is associated with a −0.79% change in HbA1c.35

Adverse effects

The main adverse effect associated with DPP-IV inhibitors is hypoglycaemia, apparent on combination with sulphonylurea. For this reason, dose reduction and caution are advised when commenced in addition to these agents. The other main adverse effects associated with DPP-IV inhibitors are shown in Table 2.

Conclusions

The use of therapeutic agents that enhance the incretin effect is an important and rapidly developing area of interest within diabetic medicine. Prior to their advent all traditional available therapies apart from metformin were associated with weight gain. Furthermore, sulphonylureas and insulin are associated with the further risk of hypoglycaemia. Newer GLP-1 mimetics are in development and phase III trials well underway with long-acting preparations such as exenatide LAR which is administered once weekly. This promising agent has shown a reduction in HbA1c of 1.4–1.7% and weight reductions up to 3.8 kg over a 15-week period.36 Incretin-based therapies offer great potential, but further experience with routine clinical practice is required and long-term evidence on benefit with regard to the micro- and macrovascular complications of T2DM.

Conflict of interest

Dr Stephens has received speaker fees from Lilly and research grant support from Novonordisk.

  • © 2010 Royal College of Physicians

References

  1. ↵
    1. Drucker DJ,
    2. Nauck MA
    The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696–705.doi:10.1016/S0140-6736(06)69705-5
    OpenUrlCrossRefPubMed
  2. ↵
    1. Joy SV,
    2. Rodgers PT,
    3. Scates AC
    Incretin mimetics as emerging treatments for type 2 diabetes. Ann Pharmacother 2005;39:110–8.doi:10.1345/aph.1E245
    OpenUrlCrossRefPubMed
  3. ↵
    1. Kendall DM,
    2. Kim D,
    3. Maggs D
    Incretin mimetics and dipeptidyl peptidase-IV inhibitors: a review of emerging therapies for type 2 diabetes. Diabetes Technol Ther 2006;8:385–96.doi:10.1089/dia.2006.8.385
    OpenUrlCrossRefPubMed
  4. ↵
    1. Shuster LT,
    2. Go VL,
    3. Rizza RA,
    4. O'Brien PC,
    5. Service FJ
    Incretin effect due to increased secretion and decreased clearance of insulin in normal humans. Diabetes 1988;37:200–3.doi:10.2337/diabetes.37.2.200
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Kreymann B,
    2. Williams G,
    3. Ghatei MA,
    4. Bloom SR
    Glucagon-like peptide-1 7–36: a physiological incretin in man. Lancet1987ii1300–4.doi:10.1016/S0140-6736(87)91194-9
    OpenUrlCrossRef
  6. ↵
    1. Meier JJ,
    2. Nauck MA
    The potential role of glucagon-like peptide 1 in diabetes. Curr Opin Investig Drugs 2004;5:402–10.
    OpenUrlPubMed
  7. ↵
    1. Efendic S,
    2. Portwood N
    Overview of incretin hormones. Horm Metab Res 2004;36:742–6.doi:10.1055/s-2004-826157
    OpenUrlCrossRefPubMed
  8. ↵
    1. Nauck MA,
    2. Kleine N,
    3. Orskov C,
    4. et al.
    Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:741–4.doi:10.1007/BF00401145
    OpenUrlCrossRefPubMed
  9. ↵
    1. Nauck MA,
    2. Heimesaat MM,
    3. Behle K,
    4. et al.
    Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 2002;87:1239–46.doi:10.1210/jc.87.3.1239
    OpenUrlCrossRefPubMed
  10. ↵
    1. Turton MD,
    2. O'Shea D,
    3. Gunn I,
    4. et al.
    A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996;379:69–72.doi:10.1038/379069a0
    OpenUrlCrossRefPubMed
  11. ↵
    1. Meier JJ,
    2. Gallwitz B,
    3. Salmen S,
    4. et al.
    Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 2003;88:2719–25.doi:10.1210/jc.2003-030049
    OpenUrlCrossRefPubMed
  12. ↵
    1. Meier JJ,
    2. Gallwitz B,
    3. Nauck MA
    Glucagon-like peptide 1 and gastric inhibitory polypeptide: potential applications in type 2 diabetes mellitus. BioDrugs 2003;17:93–102.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Keating GM
    Exenatide. Drugs 2005;65:1681–92; discussion 1693–5.doi:10.2165/00003495-200565120-00008
    OpenUrlCrossRefPubMed
  14. ↵
    1. DeFronzo RA,
    2. Ratner RE,
    3. Han J,
    4. et al.
    Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092–100.doi:10.2337/diacare.28.5.1092
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Buse JB,
    2. Henry RR,
    3. Han J,
    4. et al.
    Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628–35.doi:10.2337/diacare.27.11.2628
    OpenUrlAbstract/FREE Full Text
  16. ↵
    1. Kendall DM,
    2. Riddle MC,
    3. Rosenstock J,
    4. et al.
    Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083–91.doi:10.2337/diacare.28.5.1083
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Zinman B,
    2. Hoogwerf BJ,
    3. Durán Garcia S,
    4. et al.
    The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2007;146:477–85.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Blonde L,
    2. Klein EJ,
    3. Han J,
    4. et al.
    Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006;8:436–47.doi:10.1111/j.1463-1326.2006.00602.x
    OpenUrlCrossRefPubMed
  19. ↵
    1. Buse JB,
    2. Klonoff DC,
    3. Nielsen LL,
    4. et al.
    Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: An interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007;29:139–53.doi:10.1016/j.clinthera.2007.01.015
    OpenUrlCrossRefPubMed
  20. ↵
    1. Heine RJ,
    2. Van Gaal LF,
    3. Johns D,
    4. et al.
    Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2005;143:559–69.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Nauck MA,
    2. Duran S,
    3. Kim D,
    4. et al.
    A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 2007;50:259–67.doi:10.1007/s00125-006-0510-2
    OpenUrlCrossRefPubMed
  22. ↵
    1. Natarajan B,
    2. Edavalath M,
    3. Davies J,
    4. et al.
    Clinical experience with exenatide in a routine secondary care diabetes clinic. Prim Care Diabetes 2009;4:57–60.doi:10.1016/j.pcd.2009.11.001
    OpenUrlCrossRef
  23. ↵
    1. González C,
    2. Beruto V,
    3. Keller G,
    4. Santoro S,
    5. Di Girolamo G
    Investigational treatments for type 2 diabetes mellitus: exenatide and liraglutide. Expert Opin Investig Drugs 2006;15:887–95.
    OpenUrlCrossRefPubMed
  24. ↵
    1. Buse JB,
    2. Rosenstock J,
    3. Sesti G,
    4. et al.
    Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39–47.doi:10.1016/S0140-6736(09)60659-0
    OpenUrlCrossRefPubMed
  25. ↵
    1. Raskin P,
    2. Allen E,
    3. Hollander P,
    4. et al.
    Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 2005;28:260–5.doi:10.2337/diacare.28.2.260
    OpenUrlAbstract/FREE Full Text
    1. Marre M,
    2. Shaw J,
    3. Brändle M,
    4. et al.
    Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med 2009;26:268–78.doi:10.1111/j.1464-5491.2009.02666.x
    OpenUrlCrossRefPubMed
  26. ↵
    1. Nauck M,
    2. Frid A,
    3. Hermansen K,
    4. et al.
    Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009;32:84–90.doi:10.2337/dc08-1355
    OpenUrlAbstract/FREE Full Text
    1. Russell-Jones D,
    2. Vaag A,
    3. Schmitz O,
    4. et al.
    Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia 2009;52:2046–55.
    OpenUrlCrossRefPubMed
  27. ↵
    1. Astrup A,
    2. Rössner S,
    3. Van Gaal L,
    4. et al.
    Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009;374:1606–16.doi:10.1016/S0140-6736(09)61375-1
    OpenUrlCrossRefPubMed
  28. ↵
    1. Deacon CF
    Therapeutic strategies based on glucagon-like peptide 1. Diabetes 2004;53:2181–9.doi:10.2337/diabetes.53.9.2181
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. Ahrén B,
    2. Gomis R,
    3. Standl E,
    4. Mills D,
    5. Schweizer A
    Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004;27:2874–80.
    OpenUrlAbstract/FREE Full Text
  30. ↵
    1. Schweizer A,
    2. Couturier A,
    3. Foley JE,
    4. Dejager S
    Comparison between vildagliptin and metformin to sustain reductions in HbA(1c) over 1 year in drug-naive patients with type 2 diabetes. Diabet Med 2007;24:955–61.
    OpenUrlCrossRefPubMed
  31. ↵
    1. Rosenstock J,
    2. Baron MA,
    3. Dejager S,
    4. Mills D,
    5. Schweizer A
    Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Care 2007;30:217–23.doi:10.2337/dc06-1815
    OpenUrlAbstract/FREE Full Text
  32. ↵
    1. Charbonnel B,
    2. Karasik A,
    3. Liu J,
    4. et al.
    Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006;29:2638–43.doi:10.2337/dc06-0706
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Aschner P,
    2. Kipnes MS,
    3. Lunceford JK,
    4. et al.
    Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006;29:2632–7.doi:10.2337/dc06-0703
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. Kim D,
    2. MacConell L,
    3. Zhuang D,
    4. et al.
    Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 2007;30:1487–93.doi:10.2337/dc06-2375
    OpenUrlAbstract/FREE Full Text
Back to top
Previous articleNext article

Article Tools

Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
The incretin system in the management of type 2 diabetes mellitus
Jeffrey W Stephens
Clinical Medicine Oct 2010, 10 (5) 491-495; DOI: 10.7861/clinmedicine.10-5-491

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
The incretin system in the management of type 2 diabetes mellitus
Jeffrey W Stephens
Clinical Medicine Oct 2010, 10 (5) 491-495; DOI: 10.7861/clinmedicine.10-5-491
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • The incretin effect
    • The therapeutic potential of the incretin system in type 2 diabetes mellitus
    • Therapeutic strategies based on the incretin system
    • GLP-1 mimetics
    • DPP-IV inhibitors
    • Conclusions
    • Conflict of interest
    • References
  • Figures & Data
  • Info & Metrics

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Cardiovascular risk and prevention in diabetes mellitus
  • Microvascular complications: pathophysiology and management
Show more CME Diabetes

Similar Articles

FAQs

  • Difficulty logging in.

There is currently no login required to access the journals. Please go to the home page and simply click on the edition that you wish to read. If you are still unable to access the content you require, please let us know through the 'Contact us' page.

  • Can't find the CME questionnaire.

The read-only self-assessment questionnaire (SAQ) can be found after the CME section in each edition of Clinical Medicine. RCP members and fellows (using their login details for the main RCP website) are able to access the full SAQ with answers and are awarded 2 CPD points upon successful (8/10) completion from:  https://cme.rcplondon.ac.uk

Navigate this Journal

  • Journal Home
  • Current Issue
  • Ahead of Print
  • Archive

Related Links

  • ClinMed - Home
  • FHJ - Home
clinmedicine Footer Logo
  • Home
  • Journals
  • Contact us
  • Advertise
HighWire Press, Inc.

Follow Us:

  • Follow HighWire Origins on Twitter
  • Visit HighWire Origins on Facebook

Copyright © 2021 by the Royal College of Physicians