Patient-centric approach

Treatment choices should be individualised and culturally appropriate, and patients should have the opportunity to make informed decisions on their care and treatment options, in partnership with their healthcare providers.

GPP

Treatment choices should be individualised and culturally appropriate, and patients should have the opportunity to make informed decisions on their care and treatment options, in partnership with their healthcare providers.

GPP

The mechanism of action, advantages and disadvantages of major classes of oral glucose lowering agents are shown in Tables 2, 3

& 4 on pages 71-72.

5.4 Optimisation of glycaemic control, after initiation of therapy

Type 2 diabetes is a progressive condition in which β-cell function deteriorates with increasing duration of diabetes. Stepwise therapy with multiple pharmacological therapies is often needed over time to maintain target glucose control. Two or more oral agents, or insulin therapy either alone or in combination with oral agents, may be required.

Since there are almost always multiple defects in type 2 diabetes, the early institution of combination therapy targeting these derangements is an attractive option. However, the cost-effectiveness of this approach has not yet been well studied.

5.5 Newer agents

GLP-1 receptor (glucagon-like peptide-1) agonists

Incretin hormones are important mediators of glycaemic homeostasis.

GLP-1 (glucagon-like peptide-1) agonists were developed to mimic the effect of endogenous GLP-1 hormone, but with a longer duration

are administered via subcutaneous injections. Numerous clinical studies have confirmed the efficacy of GLP-1 agonists for improving glycaemic control with a low risk of hypoglycaemia. The predominant adverse events associated with GLP-1 agonists are gastrointestinal in nature (nausea, vomiting, diarrhea, and the use of exenatide is not recommended in patients with a history of pancreatitis).

D

The use of exenatide is not recommended in type 2 diabetes patients with a history of pancreatitis.^113-115

Grade D, Level 4

5.6 Insulin therapy

Insulin replacement therapy is required for all people with type 1 diabetes and for many with type 2 diabetes. In the latter, insulin may also be used temporarily to control hyperglycaemia during acute illness or stress. In the therapeutic journey, the progressive nature of type 2 diabetes and treatment should be explained and reinforced regularly, and progression to insulin should not be described as failure or punishment. Newer insulin therapies, including the concept of physiologic basal-bolus insulin and the availability of insulin analogues, are changing clinical diabetes care. The key to effective insulin therapy is an understanding of principles that, when implemented, can result in improved diabetes control. Unfortunately, tight glycaemic control is associated with a certain degree of risk of hypoglycaemia.

A

All patients with type 1 diabetes must receive insulin. Multiple daily injections (3 or more) or the use of continuous subcutaneous insulin infusion (CSII or insulin pump therapy) may be required to achieve target glucose levels.

Grade A, Level 1⁺

Tables 2, 3 and 4 (pg 71-72) list the common types of insulin preparations that are currently available in our local context.

B

Insulin therapy should be managed with relevant and regular insulin and hypoglycaemia-related self-management training with the common goal of improved glycaemic control and reduction in risk of severe hypoglycaemia.60, 116-119

Grade B, Level 2⁺⁺

Examples of common insulin regimens include the following:

• Twice-daily administration of one of the following regimens:

- short-acting insulin (regular/soluble insulin) or rapid-acting insulin analogue (insulin lispro or aspart), with intermediate-acting insulin, i.e. neutral protamine Hagedorn (NPH) before breakfast and before dinner, or - pre-mixed regular and (NPH) insulins, usually administered

before breakfast and before dinner, or

- pre-mixed rapid-acting insulin analogues and their protaminated intermediate-acting analogues (protaminated insulin lispro or protaminated insulin aspart) before breakfast and dinner.

• Multiple daily injections (three or more) using short-acting insulin or rapid-acting insulin analogues before meals with intermediate-acting or long-acting insulin once a day, often at bedtime (basal-bolus regimen).

• A single injection of intermediate-acting insulin or long-acting insulin/insulin analogue at bedtime combined with daytime oral agents for selected type 2 diabetic patients.

Many premixed insulin preparations (stable mixtures of fixed proportions of rapid-acting insulin analogues with protaminated insulin analogues, or short-acting insulin with intermediate-acting insulin) are available commercially. Insulin is also available in cartridges for use in special insulin pens for easy storage, dosing and administration.

The pharmacological characteristics of various types of insulins differ from each other. Insulin type and species, injection technique, site of injection and insulin antibodies can all affect the onset, degree, and

alternative to multiple daily injections, primarily in patients with type 1 diabetes.²⁵ Because of residual β-cell secretory capacity, insulin therapy regimens used in type 2 diabetic patients may be less complicated than those prescribed for patients with type 1 diabetes, although fairly similar regimens are also used in type 2 diabetics who become totally dependent on insulin.

5.7 Rapid-acting insulin analogues

Three rapid-acting insulin analogues, insulin lispro, aspart, and insulin glulisine have been developed. These demonstrate faster absorption kinetics and can therefore be injected just before meals. They also attain higher concentrations after subcutaneous injection compared to conventional human insulin and reduce post-prandial glucose to a greater extent.^120-122 The shorter duration of action of these rapid-acting insulin analogues may also lead to a lower incidence of hypoglycaemia.

5.8 Long-acting insulin analogues

Two long-acting insulin analogues, insulin glargine and insulin detemir, are available for use locally.^123-124 These long-acting analogues have virtually no plasma peak, and act for about 18-24 hours,¹²⁵ hence allowing once-daily administration as background insulin. Some patients may require twice-daily administration for effective basal therapy. The time of day at which these analogues are injected has no clinically relevant effect on glycaemic control. These new long-acting insulin analogues may provide more predictable fasting blood glucose with lower intra-subject variation and reduced risk of hypoglycaemia compared with (NPH) insulin. Patients on intermediate-acting and long-acting insulin who experience frequent hypoglycaemic episodes related to their peak activity may benefit from the use of these agents which have been shown to achieve better glycaemic control with lower incidence of hypoglycaemia.^126-128 In recent years, observations that

type 2 diabetes

MetforminInsulin secretagogues sulphonylurea

Insulin secretagogues meglitidines / Non sulphonylurea

ThiazolidinedioneAlpha-

ThiazolidinedioneAlpha-glucosidase inhibitors (AGI)

Dipeptidyl peptidase 4

(DPP-4) inhibitors

Glucagon-like peptide-1 (GLP-1) agonist

Decreased hepatic glucose production Increased pancreatic insulin secretion Increased pancreatic insulin secretionInsulin sensitizer Decreased gut carbohydrate absorption Inhibits DPP-4 activity

, prolongs

action of endogenous incretin hormones Activates (GLP-1) receptors

type 2 diabetes

MetforminInsulin secretagogues sulphonylurea

Insulin secretagogues meglitidines / Non sulphonylurea

ThiazolidinedioneAlpha-

ThiazolidinedioneAlpha-glucosidase inhibitors (AGI)

Dipeptidyl peptidase 4 (DPP-4) inhibitors

Glucagon-like peptide-1 (GLP-1) agonist 1-1.5%1-1.5%0.5-1.0%0.5-1.5%0.5-0.8%0.5-0.8%0.5-1.0% ModerateMildMildModerateNeutral MildMild MildModerateModerateMildModerate ModerateModerate ProvenProven----- Well

established modality

Well established modality---

modality---Low risk for hypoglycaemia Potential for weight reduction and improved β-cell mass/function

Im Dokument Diabetes Mellitus (Seite 72-77)