TREATMENT AND MANAGEMENT OF TYPE 2 DIABETES
Most patients with Type 2 Diabetes will require one or more oral agents to control their diabetes. Metformin is the preferred first line treatment (even in non-obese patients). Time to mono-therapy failure is of the order of 3 years but this differs a lot with factors such as ethnicity, BMI etc. Patients need to be aware that escalation of therapy is 'on the cards' and that this may include insulin. DSME is essential in providing an 'overview' of diabetes. DSME is an essential step to attaining good quality self management on a day to day basis. Education needs to be on-going life long learning.
How to Use the Stepped Approach to Type 2 Diabetes Medication: Patients with Type 2 diabetes should have their medication monitored and adjusted regularly to maintain optimal HbA1c levels. Rate of progression is variable but the algorithm should be used to optimise control. Each step involves starting/adding a new medication. Within each step, further dosage modification will be required over a variable time period. *Individualised HbA1c target is appropriate e.g. in elderly patients.

Note 1a The Usual starting dose of metformin is 500mg bd with food. If adverse GI side- effects occur, reduce to 500mg od for 2-4 weeks and titrate back up. If HbA1c remains>7-8% (53-64 mmol/mol) on metformin 500mg bd, increase the dose to 850mg bd or maximum of 2.5g in divided doses as tolerated.
Contraindications for metformin include: Severe adverse GI side-effects; renal failure (eGFR 30); severe heart failure or liver failure; very low BMI with clinical features to possibly suggest underlying Type 1 DM

Note 1b Alternative first line treatment could be a sulphonylurea (note 2a) or a DPP4 inhibitor such as sitagliptin (note 2b). If the patient is overweight (BMI ≥ 28), a glitazone such as pioglitazone could be considered (note 2c).

Note 1c Patients with particularly high HbA1c (e.g. > 9% or 75mmol/mol) at initial diagnosis, may require simultaneous commencement on metformin and a sulphonylurea in order to bring CGs under control more quickly (see note 2a) and may be able to 'wean off' the sulphonylurea, once metformin dose is titrated up and lifestyle factors are adopted.

Note 1e Add basal insulin (see starting insulin guideline, on Insulin tab)

Note 2a Add Sulphonylurea: This has been traditional second line Tx. However availability of newer agents such as sitagliptin and pioglitazone mean these agents could be considered (notes 2b/c).
All patients on sulphonylureas should be taught how to do SMBG because of risk of hypoglycaemia.
Typical starting doses are:
• Glipizide 2.5 mg od or bd and titrate after 1-2 months depending on SMBG/HbA1c. (Max. is 5-10mg bd)
• Gliclazide 40 mg od/bd and titrate after 1-2 months depending on SMBG/HbA1c. (Max. is 160mg bd).

Note 2b Sitagliptin (Januvia) 100mg od is a non-funded medication (costs approx $100 per month). Does not need to be taken with food. In combination with metformin, does not cause hypoglycaemia and is weight neutral. Dose does not require titration beyond 100mg. Use 50mg for those with eGFR between 30-50.

Note 2c Pioglitazone 30mg od. (Special Authority approval required). Should be avoided in patients with liver disease, heart disease or osteoporosis. Onset of action takes up to 6 weeks. Does not need to be taken with food. In combination with metformin, does not cause hypoglycaemia. Dose increased to 45mg od. Main side effect is moderate weight gain ~3kg partly (can be more) due to s/c fluid retention but generally well tolerated.

Note 2d Acarbose - start with 25mg with evening meal; increase to 50mg with evening meal; then 50mg 2x daily; then 50mg 3x daily. Major side effect: flatulence. NB. Special authority no longer required

Note 3a Add basal insulin (see starting insulin guideline, on Insulin tab)

Note 3b Trial of triple oral agents: This is usually only effective in patients who are just starting to fail maximum dual therapy (HbA1c < 8.5% or 70 mmol/mol).

Note 3a Byetta (Exenatide) and Victoza (Liraglutide) are an option in patients who can self-fund ($250 per month) & are willing to inject s/c bd. (Please refer these patients to the Diabetes Service)

Note 1d Newly diagnosed patients should have HbA1c checked within 3 months and medication titrated accordingly. Lifestyle advice should be reinforced and referral to DSME, Diabetes eye screening etc instigated.

Background and Introduction:
High blood pressure is very common in individuals with Type 2 diabetes.
• Up to 75% of cardiovascular complications in Type 2 diabetes are hypertension-related.
• Target BP in diabetes patients is < 130/80 but this is seldom achieved ( 140/80 in patients>75y).

Lifestyle modification is important but antihypertensive drug therapy is usually required.
Most individuals will require combination therapy. In the elderly and patients with postural giddiness, check standing and sitting blood pressure.
Treatment may need to be adjusted to avoid excessive postural hypotension (e.g. standing systolic < 100mmHg (or 120 in individuals over 70 years)*.
Referral to specialist Diabetes or Hypertension clinic may be indicated.

The basic principle of blood pressure management in Type 2 diabetes is to achieve target blood pressure with a regimen which includes a reasonable dose of ACE-inhibitor (or ARB (antagonist) eg. Candesdartan or Losartan in ACE-intolerant patients).

These, calcium channel blockers and thiazide diuretics are the three most important antihypertensive drug classes, and are often required in combination.

To expedite blood pressure control it is a reasonable option to start patients with stage 2 hypertension (>150/90) on 2 antihypertensive drugs simultaneously (apart from in patients aged over 70y)*.

* Elderly patients require commencement on lower doses of blood pressure medications & a more gentle titration.

NOTES TO ACCOMPANY LIPID GUIDELINE FOR TYPE 2 DIABETES
Multiple clinical trials have demonstrated significant beneficial effects of statin therapy on CVD outcomes in subjects with Type 2 diabetes. The evidence for important CVD event benefit of drugs that primarily raise HDL or lower TG is weak (ADA). Ezetimibe modestly lowers LDL but there is no trial evidence showing a reduction in CVD events.

In those with known CVD or those patients over the age of 40 with another CVD risk factor (eg smoking, hypertension, microalbuminuria), a statin should be added regardless of baseline lipid levels (Heart Protection study). It is estimated that about 80% of patients with Type 2 diabetes will fall into this category.

There is little clinical trial evidence of benefit for patients with Type 2 diabetes under the age of 40 or for Type 1 diabetes patients, but statin treatment of Type 1 diabetes patients aged over 40 years, especially with another cardiovascular risk factors, should be strongly considered. Use Risk Tables (modified for diabetes) for others, and clinical acumen.

In those who have risk factors but without known CVD, the minimum aim is to lower LDL to less than 2.5mmol/L (although Canadian Diabetes Assn. and NZ Cardiovascular Guidelines say less than 2.0 mmol/L). Alternatively, one might aim for at least a 30- 40% reduction from pre-treatment level, and/or a Total Cholesterol /HDL ratio of less than 4.0. In those with a previous cardiovascular event a target LDL of less than 1.7mmol/L is appropriate given a further reduction in events with more aggressive LDL lowering.

Maori and Pacific Island patients consider starting statins earlier for those who appear to have increased CV risk independent of traditional risk factors.

Optimal lipid levels for people with Diabetes
Total Cholesterol < 4.0 mmol/L
LDL Cholesterol < 2.0 mmol/lL
HDL Cholesterol ≥ 1.0 mmol/L
Triglycerides <1.7 mmol/L
(NZ Cardiovascular Guidelines)

Note 1: Intolerant of statins?
Myalgia, with or without plasma creatine kinase (CK) elevations.
If CK more than 5x upper limit of normal the statin should be stopped.
Once asymptomatic and CK is reduced (if it was elevated) cholesterol goals can be approached by:
a. using a different statin e.g. Simvastatin, starting on a low dose and titrate up
b. use an alternate daily or twice weekly more potent statin e.g. atorvastatin, rosuvastatin
c. the combination of the lowest tolerated statin plus a cholesterol absorption inhibitor (Ezetimibe)
Creatine Kinase [CK] Normal Ranges: Male: 60 – 220 and Female: 30 - 180

Combinations severe fasting hyper triglyceridemia (note 2a),
High LDL and TG (note 2b), Low HDL with LDL TG on target(note 2c)

Note 2a For patients with severe fasting hyper triglyceridemia review secondary causes (e.g. alcohol, hypothyroidism, renal or liver disease) and consider treatment with fibrate if TG more than 4.5mmol/L. Most commonly, Bezalip Retard 400mg is used in New Zealand (assuming eGFR>50ml/min). Monitoring of renal function is appropriate with use of this drug.

Note 2b In patients with a combination of high LDL and TG, use a statin first and then : If high C/V risk consider fibrate and statin if fasting TG more than 2.5 mmol/L, but beware of increased risk of myositis when these drugs used together. If high C/V risk consider ezetimibe and statin if LDL not at target or not at least 30% lower than baseline (note access criteria for this drug are under review).

Note 2c If low HDL-C (with LDL-C &TG at target)
a. Optimise LDL Chlol. Though HDL-C is a C/V risk there is little evidence that raising HDL lowers C/V events.
b. Prescribe statin followed if required by bezafibrate if TG above target
c. Weight loss will usually increase HDL