Page 29 - World of Irish Nursing April 2018

48 Diabetes

of drugs that prolong the action of reabsorption is blocked, and glycosuria is it was associated with fewer nocturnal
incretin hormones. DPP-4 degrades increased. hypoglycaemic episodes than glargine,
numerous biologically active peptides, The change in the renal glucose thresh- with no change in the overall glycaemic
including the endogenous incretins GlP-1 old is likely to be behind the low rate control. 7
and glucose-dependent insulinotropic pol- of hypoglycaemia seen with SGlT2 Ensuring adherence to treatment
ypeptide (GIP). DPP-4 inhibitors can be inhibitors. The prevalence of type 2 diabetes is
used as a monotherapy or in combination The mechanism of action is insulin- increasing in Ireland due to the ageing
with metformin or a TZD. They are given independent, which makes SGlT2 population and increase in obesity. A
once daily and are weight neutral. inhibitors complementary to other glu- multidisciplinary approach for the man-
GLP-1 agonists (ie. exenatide, liraglutide, cose-lowering treatments. Average agement of diabetes includes involving the
dulaglutide): GlP1 is secreted in response HbA1c reduction afforded by SGlT2 inhib- patient.
to food intake and stimulates insulin itors when used as monotherapy or as an Successful treatment of type 2 diabe-
release, reduce glucagon, and slow gastric add-on to metformin is 0.32% to 1.17%. tes is often complicated by the inevitably
emptying. GlP-1 agonists are easy to use, As with other type 2 diabetes therapies, progressive nature of the condition and
as they are characterised by fixed doses greater HbA1c reduction is observed with the need to balance target blood glucose
and flexibility in time of administration higher baseline levels. Average weight levels against an increased risk of treat-
(except exenatide). loss recorded in clinical trials was 1.5-3kg ment-related adverse effects such as
The glucose-dependent mechanism of compared with placebo; however, weight hypoglycaemia and weight gain.
action, and the resultant lack of hypo- loss tends to plateau, and some patients All patients with diabetes need full
glycaemia is a major advantage which regain lost weight. initial assessment and regular review
increases the safety of these drugs, Adverse events include polyuria, gen- to ensure that they are achieving their
while maintaining efficacy. Weight loss itourinary infections, hypotension, bone target HbA1c. They should be monitored
5
with liraglutide and exenatide, and lack fractures, and diabetic ketoacidosis. With for CV risk factors and microvascular
of weight gain with DPP-4 inhibitors is regard to the latter, the American Associ- complications.
another factor which encourages use of ation of Clinical endocrinologists (AACe) A lifestyle intervention programme to
this class of drugs. GlP-1 receptor ago- and American College of endocrinology promote weight loss and increase activity
nists aid weight loss, and liraglutide was (ACe) convened a conference in october levels should be included as part of diabe-
recently licensed for individuals without 2015 to review the clinical data. An expert tes management. Adherence to treatment
diabetes as a weight loss treatment. A consensus statement was issued noting is often compromised by the fear of hypo-
6
common side-effect of GlP-1 receptor that the incidence of diabetic ketoacidosis glycaemia and weight gain, and therefore
agonists is nausea, which is usually tem- to be ‘infrequent’, requiring no change in patient education is a vital aspect of
porary and disappears around two weeks recommendations. 7 management. Most patients require com-
after treatment initiation. In addition, Newer insulins bination glucose-lowering agents and
GlP-1 receptors also increase satiety and longer-acting insulins have been devel- many patients will require insulin.
augment weight loss. At present, GlP-1 oped to provide a more stable basal insulin Poochellam Muthalagu is a consultant endocrine physician
7
receptor agonists are only available in an profile over a 24-hour period. The action at Cavan General Hospital
injectable form. of insulin can be delayed by increasing its
The lack of other major side-effects such molecular size and slowing its absorption. References
1. Look AHEAD Research Group. Reduction in weight and
as oedema and GI disturbance with DPP-4 Degludec is formed of hexameric chains cardiovascular disease risk factors in individuals with
inhibitors is another advantage. The incre- that slowly separate, releasing the active type 2 diabetes: one-year results of the Look AHEAD trial.
tin-based therapies can be used in mild to monomer that can then be absorbed. In Diabetes Care. 2007; 30:1374-1383
2. King P, Peacock I & Donnelly R. The UK Prospective
moderate renal failure with appropriate clinical trials, in patients with type 2 dia- Diabetes Study (UKPDS): clinical and therapeutic
dose adjustments, and can be given to betes, it was non-inferior to glargine and implications for type 2 diabetes. Br J Clin Pharmacol
1999; 48(5):643-648
elderly patients. had lower levels of hypoglycaemic epi- 3. American Diabetes Association. Implications of the
Newer therapies targeting renal glu- sodes, particularly at night (nocturnal United Kingdom Prospective Diabetes Study. Diabetes
cose handling hypoglycaemia). Care 2000; 23(1):S27-31
7
4. Campbell IW. The UK Prospective Diabetes Study
Sodium glucose cotransporter-2 inhibitors The long half-life of degludec com- (UKPDS): Its legacy for type 2 diabetes management.
SGlT2 inhibitors (eg. dapagliflozin, pared with traditional, long-acting insulins Prim Care Cardiovasc J, 2009; 2(1):48-49
canagliflozin, empagliflozin), the newest means that patients can be much more 5. Tran L, Zielinski A, Roach AH et al. The pharmacologic
treatment of type 2 diabetes: oral medications. Ann
antihyperglycaemic drug class, have flexible about the timing of their basal Pharmacotherapy, 2015; 49(5):540-556
6. Prasad-Reddy L, Isaacs D. A clinical review of GLP-1
a novel mechanism of action. Instead
insulin doses, without compromising their
WiN Vol 26 No 3 april 2018 involved in the digestive process, this people with erratic lifestyles. Glargine 7. Pi-Sunnier X, Satrap A, Guijosa K, et al. A randomized,
receptor agonists: efficacy and safety in diabetes and
glycaemic control.
of inhibiting hormones and enzymes
beyond. Drugs Context. 2015; 4:212283
This may be particularly useful for
controlled trial of 3.0 mg of liraglutide in weight
new drug class targets the SGlT2 protein,
management. NEJM 2015; 373(1): 11-22
which is located on the proximal renal
U300 is a more concentrated form of
8. Handelsman Y, Henry RR, Bloomgarden ZT, et al.
American Association of Clinical Endocrinologists and
insulin glargine available as 300 units/ml
tubules.
American College of Endocrinology position statement
By inhibiting SGlT2, the renal thresh-
in a pre-filled pen. U300 also has a longer
on the association of SGLT-2 inhibitors and diabetic
old for glucose is reduced, renal glucose
half-life compared with glargine. In trials,
ketoacidosis. Endocr Pract 2016; 22:753-762