SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 11 NUMBER 1 • MARCH 2014
31
Current management of a patient with diabetes involves reducing
cardiovascular risk factors and treating vascular complications
in addition to glycaemia. GLP-1-based therapies offer a distinct
advantage over other drugs for type 2 diabetes because of the effect
on the overall metabolic profile. Preservation of beta-cell mass and
improvement in microvascular complications of diabetes has been
noted in animal models of GLP-1-based treatment. If these results
are replicated in human studies it will be a huge step forward in the
clinical management of diabetes.
Declaration of conflicting interest
The authors declare that there is no conflict of interest.
Funding
This research received no specific grant from any funding agency in
the public, commerial, or not-for-profit sectors.
References
1. Holst JJ and Orskov C. Incretin hormones – An update.
Scand J Clin Lab Invest
2001;
234
: S75–85.
2. Nauck MA, Homberger E, Siegel EG
et al
. Incretin effects of increasing glucose
loads in man calculated from venous insulin and C-peptide responses.
J Clin
Endocrinol Metab
1986;
63
: 492–498.
3. Nauck M, Schmidt WE, Ebert R
et al
. Insulinotropic properties of synthetic human
gastric inhibitory polypeptide in man: Interactions with glucose, phenylalanine,
and cholecystokinin- 8.
J Clin Endocrinol Metab
1989;
69
: 654–662.
4. Nauck MA, Bartels E, Orskov C
et al
. Additive insulinotropic effects of exogenous
synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-
(7–36) amide infused at near-physiological insulinotropic hormone and glucose
concentrations.
J Clin Endocrinol Metab
1993;
76
: 912–917.
5. Vilsbøll T, Krarup T
et al
. Both GLP-1 and GIP are insulinotropic at basal and
postprandial glucose levels and contribute nearly equally to the incretin effect
of a meal in healthy subjects.
Regul Pept
2003;
114
: 115–121.
6. Meier JJ, Nauck MA, Kranz D
et al
. Secretion, degradation, and elimination
of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with
chronic renal insufficiency and healthy control subjects.
Diabetes
2004;
53
:
654–662.
7. Sam AH, Troke RC, Tan TM
et al
. The role of the gut/ brain axis in modulating
food intake.
Neuropharmacology
2012;
63
: 46–56.
8. Marks V. The contribution made by clinical biochemistry to the understanding
and treatment of diabetes: A personal perspective.
Br J Diabetes Vasc Dis
2012;
12
: 285–289.
9. Martin GR and Wallace LE, Sigalet DL. Glucagon-like peptide-2 induces
intestinal adaptation in parenterally fed rats with short bowel syndrome.
Am J
Physiol Gastrointest Liver Physiol
2004;
286
: G964–972.
10. Prasad R , Alavi K, and Schwartz MZ. Glucagon-like peptide-2 analogue
enhances intestinal mucosal mass after ischemia and reperfusion.
J Pediatr Surg
2000;
35
: 357–359.
11. Prasad R, Alavi K and Schwartz MZ. GLP-2alpha accelerates recovery of mucosal
absorptive function after intestinal ischemia/reperfusion.
J Pediatr Surg
2001;
36
: 570–572.
12. Ahrén B, Landin-Olsson M, Jansson PA
et al
. Inhibition of dipeptidyl peptidase-4
reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2
diabetes.
J Clin Endocrinol Metab
2004;
89
: 2078–2084.
13. HermanGA,StevensC,VanDyckK
etal
.Pharmacokineticsandpharmacodynamics
of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: Results
from two randomized, double-blind, placebo-controlled studies with single oral
doses.
Clin Pharmacol Ther
2005;
78
: 675–688.
14. Drucker DJ and Nauck MA. The incretin system: Glucagon-like peptide-1
receptor agonists and dipeptidyl peptidase-4 inhibitors in Type 2 diabetes.
Lancet
2006;
368
: 1696–1705.
15. IW Campbell, C Day. Sitagliptin — enhancing incretin action.
Br J Diabetes Vasc
Dis
, 2007,
7
: 134–139.
16. Körner M, Stöckli M, Waser B
et al.
GLP-1 receptor expression in human tumors
and human normal tissues: Potential for in vivo targeting.
J Nucl Med
2007;
48
:
736–743.
17. Parks M and Rosebraugh C. Weighing risks and benefits of liraglutide – The
FDA’s review of a new antidiabetic therapy.
N Engl J Med
2010;
362
: 774–
777.
18. Nauck M, Frid A, Hermansen K
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.
19. Garber A, Henry R, Ratner R
et al.
Liraglutide versus glimepiride monotherapy
for Type 2 diabetes (LEAD-3 Mono): A randomised, 52-week, phase III, double-
blind, parallel-treatment trial.
Lancet
2009;
373
: 473–481.
20. Madsbad S. Treatment of Type 2 diabetes with incretinbased therapies.
Lancet
2009;
373
: 438–439.
21. Russell-Jones D, Vaag A, Schmitz O
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
: 2046–2055.
22. Gill A, Hoogwerf BJ, Burger J
et al
. Effect of exenatide on heart rate and blood
pressure in subjects with Type 2 diabetes mellitus: A double-blind, placebo-
controlled, randomized pilot study.
Cardiovasc Diabetol
2010;
9
: 6. Online only.
DOI:10.1186/1475-2840-9-6.
23. Barragán JM, Eng J, Rodríguez R
et al.
Neural contribution to the effect of
glucagon-like peptide-1-(7–36) amide on arterial blood pressure in rats.
Am J
Physiol
1999;
277
: E784–791.
24. Crajoinas RO, Oricchio FT, Pessoa TD
et al.
Mechanisms mediating the diuretic
and natriuretic actions of the incretin hormone glucagon-like peptide-1.
Am J
Physiol Renal Physiol
2011;
301
: F355–363.
25. Kim M, Platt MJ, Shibasaki T
et al.
GLP-1 receptor activation and Epac2 link atrial
natriuretic peptide secretion to control of blood pressure.
Nat Med
2013;
19
:
567–575.
26. Gaspari T, Liu H, Welungoda I
et al
. A GLP-1 receptor agonist liraglutide inhibits
endothelial cell dysfunction and vascular adhesion molecule expression in an
ApoE- /- mouse model.
Diabetes Vasc Dis Res
2011;
8
: 117–124.
27. Okerson T, Chilton RJ. The cardiovascular effects of GLP-1 receptor agonists.
Cardiovasc Ther
2012;
30
: e146–155.
28. Robinson LE, Holt TA, Rees K
et al
. Effects of exenatide and liraglutide on heart
rate, blood pressure and body weight: Systematic review and meta-analysis.
Br
Med J Open 2
013;
3
: doi: 10.1136/bmjopen-2012–001986.
29. Nikolaidis LA, Mankad S, Sokos GG
et al.
Effects of glucagon-like peptide-1 in
patients with acute myocardial infarction and left ventricular dysfunction after
successful reperfusion.
Circulation
2004;
109
: 962–965.
30. Lønborg J, Vejlstrup N, Kelbæk H
et al
. Exenatide reduces reperfusion injury in
patients with ST-segment elevation myocardial infarction.
Eur Heart J
2012;
33
:
1491–1499.
31. Gao H, Kiesewetter DO, Zhang X
et al
. PET of glucagon-like peptide receptor
upregulation after myocardial ischemia or reperfusion injury.
J Nucl Med
2012;
53
: 1960–1968.
32. Sokos GG, Nikolaidis LA, Mankad S
et al
. Glucagon-like peptide-1 infusion
improves left ventricular ejection fraction and functional status in patients with
chronic heart failure.
J Card Fail
2006;
12
: 694–699.
33. Moberly SP, Mather KJ, Berwick ZC
et al
. Impaired cardiometabolic responses to
glucagon-like peptide 1 in obesity and Type 2 diabetes mellitus.
Basic Res Cardiol
2013;
108
: 365. Online only. DOI: 10.1007/s00395-013-0365-x.
34. Pannacciulli N, Le DS, Salbe AD
et al
. Postprandial glucagon-like peptide-1 (GLP-1)
response is positively associated with changes in neuronal activity of brain areas
implicated in satiety and food intake regulation in humans.
Neuroimage
2007;
35
: 511–517.
35. Shaw JE, Sicree RA and Zimmet PZ. Global estimates of the prevalence of diabetes
for 2010 and 2030.
Diabetes Res Clin Pract
2010;
87
: 4–14.
36. Vinciguerra F, Baratta R, Farina MG
et al
. Very severely obese patients have a high
prevalence of Type 2 diabetes mellitus and cardiovascular disease.
Acta Diabetol
2013;
50
: 443–449.
37. Jin HY, Liu WJ, Park JH
et al
. Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor
(Vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats.
Arch
Med Res
2009;
40
: 536–544.
38. Bertilsson G, Patrone C, Zachrisson O
et al
. Peptide hormone exendin-4 stimulates
subventricular zone neurogenesis in the adult rodent brain and induces recovery
in an animal model of Parkinson’s disease.
J Neurosci Res
2008;
86
: 326–338.
39. McClean PL, Parthsarathy V, Faivre E
et al.
The diabetes drug liraglutide prevents
degenerative processes in a mouse model of Alzheimer’s disease.
J Neurosci
2011;
31
: 6587–6594.
40. Porter DW, Kerr BD, Flatt PR
et al.
Four weeks administration of Liraglutide
improves memory and learning as well as glycaemic control in mice with high fat
dietaryinduced obesity and insulin resistance.
Diabetes Obes Metab
2010;
12
:
891–899.
41. Gault VA, Porter WD, Flatt PR
et al.
Actions of exendin-4 therapy on cognitive
function and hippocampal synaptic plasticity in mice fed a high-fat diet.
Int J
Obes
2010;
34
: 1341–1344.
42. Isacson R, Nielsen E, Dannaeus K
et al
. The glucagon-like peptide 1 receptor
agonist exendin-4 improves reference memory performance and decreases
immobility in the forced swim test.
Eur J Pharmacol
2011;
650
: 249–255.
