PHARMAC and long-acting insulin analogues: a poor man’s
insulin pump—but not available to the poor man
Insulin glargine is a long-acting insulin analogue
providing a more predictable and reproducible circulating insulin profile than
other available basal insulin products. Hypoglycaemia is one of the main
limiting factors to patients with diabetes requiring insulin, in achieving tight
glycaemic control and reduced rates of complications. Evidence from randomised
controlled clinical trials demonstrates reduced rates of hypoglycaemia in
patients with type 1 and type 2 diabetes using insulin glargine compared with
other basal insulin. Insulin glargine has been registered for use in New Zealand
since June 2001, but currently remains unsubsidised by PHARMAC. Reducing the
incidence and impact of diabetes is one of the stated aims in the New Zealand
Health Strategy and the complete lack of funding for pharmaceutical agents such
as insulin glargine severely limits its accessibility to patients with diabetes
and would seem in contradiction to this aim.
Insulin glargine (Lantus)
Treatment of type 1 and type 2 diabetes
Both type 1 and type 2 diabetes are associated with micro
and macro-vascular complications. Diabetes is the most common cause of blindness
and renal failure requiring dialysis in New Zealand. However, maintaining tight
glycaemic control has been shown to reduce the rates of diabetes related
complications in both type 11 and type 2 diabetes.2 This forms the basis of
management guidelines advocating HbA1c targets of 6.5–7.0%.
Hypoglycaemia is the main limiting factor for individuals
with type 1 diabetes or those with type 2 diabetes using insulin in achieving
Hypoglycaemia results from excess circulating insulin
dissociated from food intake and can be particularly problematic when occurring
overnight. Hypoglycaemia is what patients with diabetes fear the most and can
have profound effects on work capacity, efficiency, and lifestyle in general.
Recurrent unexplained hypoglycaemia often limits patients’ willingness to
attempt to achieve better control.
Conventional management of type 1 diabetes utilises one or
two injections of intermediate or long-acting insulin such as NPH insulin
(insulin isophane), with mealtime injection of short-acting insulin, currently
most commonly with a rapid-acting insulin analogue.
Limitations to achieving tight glycaemic control with this
regimen include the peak effect of NPH insulin which occurs 4-6 hours after
injection and the intra-individual variability in circulating insulin profile
following injection of NPH insulin. This often creates an unpredictable excess
insulin action overnight and/or several hours post-prandially contributing to
episodes of hypoglycaemia.
Insulin glargine is a long-acting human insulin analogue
which provides a once-daily basal insulin with a more predictable and
reproducible circulating insulin profile than other available basal insulin
products.3 The profile of Glargine is similar to that achieved with a continuous
subcutaneous insulin infusion (insulin pump) and has been dubbed “the poor
Glargine reduces fasting plasma glucose and reduces the
frequency of both nocturnal and daytime hypoglycaemic episodes in individuals
with type 1 diabetes who are achieving good glycaemic control.3 Additionally,
meta-analyses in type 2 diabetes show reduced nocturnal hypoglycaemia and
improved glycaemic control with glargine compared with NPH insulin.4
The New Zealand Health Strategy
identifies diabetes as one of the 13 population health objectives stating an
aim: “To reduce the incidence and impact of diabetes”.5
Glargine has been registered and approved for use in New
Zealand since June 2001, however is not funded by PHARMAC. Glargine is available
on prescription through community pharmacies.
An application was made to PHARMAC on 13 July 2004 for
consideration by PTAC. A decision was deferred to the Diabetes Subcommittee
which did not meet until May 2005. The minutes of this meeting indicate the
“...recommended that insulin glargine should be listed
on the Pharmaceutical Schedule with Special Authority for subsidy criteria that
would target treatment to the following patient groups:
Treatment of patients with type 1 diabetes receiving an
intensive regimen (injections at least three times a day) of an intermediate or
long acting insulin in combination with a rapid acting insulin analogue for at
least three months who have experienced:
- (a) More
than one unexplained severe hypoglycaemic episode in the previous 12 months
(severe defined as requiring the assistance of another person);
- (b) Unexplained
symptomatic nocturnal hypoglycaemia biochemically documented at <3.0 mmol/L,
more than once a month despite optimal management;
- (c) Poor
glycaemic control (HbA1c ≥ 8.0%) where attempts a dose escalation have
been precluded due to documented frequent symptomatic hypoglycaemia associated
with a decrease in quality of life; or
- (d) Poor
glycaemic control (HbA1c ≥ 8.0%).”
Subcommittee considered that insulin glargine should be funded under criteria
(a) and (b) with a high priority, under (c) with a moderate priority and (d)
with a low priority. This now allows the pharmaceutical company to enter into
negotiations with PHARMAC for subsidisation of insulin glargine.
A vial of Glargine containing 1000 IU insulin has a
ex-manufacturer price of NZ$84.06 (8.4c per unit). This compares with a vial of
NPH insulin containing 1000 IU of NZ$17.68 (1.8c per unit). However, the
majority of patients on insulin use an insulin pen device for administration of
insulin. The equivalent comparison is a penfill vial of 300IU Glargine each at
NZ$25.22 (8.4c per unit) or a penfill vial of 300IU NPH insulin at NZ$5.97 (2.0c
Glargine is widely available worldwide. In the United
Kingdom, Glargine was assessed by NICE (National Institute of Clinical
Excellence) in 2002 and recommended as a treatment option for people with type 1
diabetes.6 In addition it is recommended for consideration in selected patients
with type 2 diabetes, but not for routine use in this group. There are no
funding restrictions to Glargine in the UK. Glargine is available in the United
States on insurance funded managed care systems. In Australia, negotiations are
ongoing between the pharmaceutical company and funding bodies.
Whilst the rigorous assessment of clinical efficacy and
safety as well as pharmacoeconomics of any new pharmaceutical agent is
important, this should be conducted in a timely fashion. The current process as
applied to insulin glargine is creating considerable delay in making this agent
available to patients with diabetes in New Zealand who are unable to meet the
full cost. Furthermore, it is likely to make it unavailable to many who would
derive quality-of-life benefit if not benefit defined by the clinical endpoints
likely to be required by PHARMAC.
The Special Authority system for access to pharmaceuticals
creates time-consuming additional paperwork for busy clinicians which can create
a barrier to access for patients to receive pharmaceuticals from which they
would benefit. In some instances the criteria are ambiguous and in others
impractical to follow in routine clinical practice.
For an agent such as insulin glargine, where the patient
group who may receive it is small and well defined, would it not be reasonable
to allow more general access, with clear guidelines as to its recommended use?
At the risk of being accused of patch protection, as many general practitioners
may feel that they do not have the necessary experience to differentiate those
most likely to benefit, a possible approach could be to restrict Glargine to
specialist only prescription or initiation.
The New Zealand Health Strategy highlights both obesity and
diabetes as priority areas. In contradiction to this, the current funding
situation for therapies and pharmaceuticals for the management of obesity and
diabetes in New Zealand provides an environment for physicians rather like NASA
trying to send the Space Shuttle Discovery into orbit with a IBM486 chip and no
broadband internet access.
There is no funding for pharmaceuticals such as orlistat or
sibutramine, no funded bariatric surgery, limited funding of insulin pumps,
limited access to thiazolidinediones and currently no funding for insulin
glargine. With an exciting array of new agents on the horizon for obesity and
diabetes management what hope has the poor man got in New Zealand for Pentium 4
interest: Dr Krebs has received support to attend meetings from Aventis,
GlaxoSmithKline, Eli Lilly, and Novo Nordisk.
Jeremy Krebs, Department of Endocrinology, Wellington Hospital,
Jeremy Krebs, Department of Endocrinology, Wellington Hospital, Private Bag
7902, Wellington. Fax (04) 385 5819; email: email@example.com
Diabetes Control and Complications Trial Research Group. The effect of intensive
treatment of diabetes on development and progression of long-term complications
in insulin-dependent diabetes mellitus. N Engl J Med.
UPDSG. Intensive blood-glucose control with sulphonylureas or insulin compared
with conventional treatment and risk of complications in patients with type 2
diabetes (UKPDS 33). Lancet. 1998;352:837–53.
CJ, Plosker GL, Keating GM, et al. Insulin Glargine: An updated review of its
use in the management of diabetes mellitus. Drugs. 2003;63:1743–78.
J, Bendetti MM, Haring H-U. Confirmed lower risk of hypoglycaemia with insulin
glargine versus NPH insulin: a meta-analysis of 2304 patients with type 2
diabetes. In: 63rd Annual Scientific Sessions of the American Diabetes
Association; 2003 Jun 13–17; New Orleans, Louisiana; 2003, Jun
of Health. The New Zealand Health Strategy. Wellington: Ministry of Health;
2000. Available online. URL: http://www.moh.govt.nz/moh.nsf/0/c024d8d149d4c168cc2569b1007679ca?OpenDocument
Accessed August 2005.
Institute for Clinical Excellence. Guidance on the use of long-acting insulin
analogues for the treatment of diabetes: insulin glargine. Technical appraisal
guidance 2002; No 53.