- Email: [email protected]
Sulphonyurea as a cause of severe hypoglycaemia in the community
p r i m a r y c a r e d i a b e t e s 4 ( 2 0 1 0 ) 61–63
Contents lists available at ScienceDirect
Primary Care Diabetes journal homepage: http://www.elsevier.com/locate/pcd
Brief report
Sulphonyurea as a cause of severe hypoglycaemia in the community Jen M. Ng ∗ , Duane D. Mellor, Ewan A. Masson, Belinda J. Allan Diabetes Centre, Michael White Centre, Hull Royal Infirmary, 220-226 Anlaby Road, Hull HU3 2RW, United Kingdom
a r t i c l e
i n f o
a b s t r a c t
Article history:
Introduction: Hypoglycaemia is a well recognised side effect of insulin and sulphonyurea
Received 12 October 2009
therapy in the treatment of, patients with diabetes mellitus.
Received in revised form
Methods: We performed a retrospective analysis of patients who developed severe hypogly-
14 December 2009
caemia in Hull and, East Yorkshire, United Kingdom over a 4-month period to assess the
Accepted 15 December 2009
different therapies that contribute the most to the problem and the patient groups who are
Available online 12 January 2010
at greatest risk. Results: Of the 75 patients with diabetes mellitus who developed severe hypoglycaemia, 61
Keywords:
(80%) were taking, insulin, 5 in combination with metformin. Ten (13%) patients were taking
Hypoglycaemia
SU therapy; 5 in, combination with metformin, 2 in combination with a thiazolidinedione
Sulphonylurea
and 1 in combination with, insulin. When the SU-treated and non-SU treated groups were compared, patients taking SU therapy were, significantly older and had significantly lower HbA1c levels. Conclusions: All patients taking SU and insulin treatment are potentially at risk of developing hypoglycaemia. Our, analysis shows that almost 15% of patients in our region who suffered from severe hypoglycaemia, were on SU therapy. Patients in this group were older and had lower levels of HbA1c. Whilst national HbA1c targets may be useful for clinicians to define glycaemic targets for their, population, this has to be tempered by what is in the best interests of the patient and not what is, dictated by the Quality and Outcomes Framework. Possible alternatives to SU therapy should be, considered especially if hypoglycaemia is a concern. © 2009 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
1.
Introduction
Hypoglycaemia is a well recognised side effect of insulin and sulphonyurea therapy in the treatment of patients with diabetes mellitus. Recent National Institute for Health and Clincial Excellence (NICE) clinical guidelines recommend that patients with Type 2 Diabetes Mellitus (T2DM) are given advice regarding hypoglycaemia when starting
∗
insulin or sulphonylurea (SU) therapy [1]. SU and insulin therapy have been associated with an increased risk of hypoglycaemia particularly in a population who have tight glycaemic control [2,3]. We performed a retrospective analysis of patients who developed severe hypoglycaemia in Hull and East Yorkshire, United Kingdom over a 4-month period to assess the different therapies that contribute the most to the problem and the patient groups who are at greatest risk.
Corresponding author. Tel.: +44 01482 675314; fax: +44 01482 675395. E-mail address: [email protected] (J.M. Ng). 1751-9918/$ – see front matter © 2009 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.pcd.2009.12.001
62
2.
p r i m a r y c a r e d i a b e t e s 4 ( 2 0 1 0 ) 61–63
Methods
All episodes of hypoglycaemia which involve the ambulance service in our Trust are reported to the local diabetes service within 72 h with patient consent. Hypoglycaemic episodes that occur in the hospital A&E are fed back within 72 h to enable rapid patient review and follow up. We included all reported episodes of severe hypoglycaemia from these sources over the period of December 2008 to March 2009 inclusive. We defined severe hypoglycaemia in this case as any hypoglycaemic event that required the intervention of the emergency services.
structured education (‘Living With Diabetes’) which includes education on the side effects of common treatments for type 2 diabetes (including SUs). However, this education is not necessarily given at a point when SU initiation is being considered. One patient on SU therapy (10%) received education on hypoglycaemia recognition and treatment but only because he was being commenced on insulin. Virtually all patients receiving SU treatment would have had this initiated in primary care and it was not possible for us to assess what information had been given to the patient at this point regarding hypoglycaemia recognition and treatment.
4. 3.
Discussion
Results
A total of 76 patients suffered severe hypoglycaemia over the 4-month study period. Seventy-three episodes occurred at patient’s residences (i.e. home, residential home, etc.) whilst 3 episodes occurred outside. There were no other serious adverse events associated with the hypoglycaemic event. The median age of patients was 63 years (IQR 43–78 years); 40 were male and 36 female. The median HbA1c was 8.1 ± 0.3 SE%. Thirty-one (40.7%) patients had type 1 diabetes (T1DM) and 33 (43.4%) had T2DM. In 11 (14.4%) cases diabetes type was not recorded. One patient without diabetes suffered hypoglycaemia due to liver failure and was excluded from the study. Of the 33 patients with T2DM, 23 (69.7%) were taking insulin of which 5 (15.1%) were in combination with metformin. Ten (30.3%) patients were taking SU therapy; 5 (15.1%) in combination with metformin, 2 (6%) in combination with a thiazolidinedione and 1 (3%) in combination with insulin. Therapy in 3 patients was not recorded. No patient presented more than once during the study period. The results of the analysis are summarised in Table 1. All HbA1c readings were obtained within 3 months of the hypoglycaemic event. When the SU-treated and non-SU treated groups were compared, patients taking SU therapy were significantly older and had significantly lower HbA1c levels. Five patients in the SU group had HbA1c levels < 6.0%. All patients taking SU and insulin treatment are potentially at risk of developing hypoglycaemia [2,3]. Our analysis shows that almost 15% of patients in our region who suffered from severe hypoglycaemia were on SU therapy. Patients in this group were older and had lower levels of HbA1c. Prior to commencing insulin therapy, all patients receive education on the recognition and management of hypoglycaemia from the diabetes specialist nurse. In our area, all patients newly diagnosed with type 2 diabetes are offered
It has been suggested that a lower HbA1c may increase an individual’s risk of cardiac death [4], particularly in the later stages of their disease. In addition, the risk: benefit of tight glycaemic control appears to potentially favour risk in those aged 75 or more [5] in terms of falls and may not improve life expectancy [6] or quality of life. The personal as well as the financial cost associated with morbidity secondary to severe hypoglycaemia must also be considered. Whilst national HbA1c targets may be useful for clinicians to define glycaemic targets for their population, this has to be tempered by what is in the best interests of the patient and not necessarily what is dictated by the Quality and Outcomes Framework. The NICE guidance recommends that patients try to maintain their target HbA1c but recognises that this target may be above the recommended national target [1]. It is therefore vital that clinicians responsible for diabetes management are ready to strike a balance between good glycaemic control whilst taking into consideration potential side effects and the impact this may have on the individual concerned. The importance of patient education in recognising and treating hypoglycaemia is vital. The importance of patient education in recognising and treating hypoglycaemia is vital. Healthcare professionals initiating any therapy for diabetes mellitus must be aware of the potential side effects and counsel patients accordingly. All patients who are commenced on insulin therapy are referred for education with the diabetes specialist nurse. Similarly, education should be a consideration prior to commencing patients on medications that can evoke hypoglycaemia in particular SU therapy due to its potentially severe side effects. The emergence of new therapies in the treatment of T2DM such as gliptins and GLP-1 analogues in combination with conventional oral agent glucose-lowering therapy have lower risks of hypoglycaemia. Therefore these therapies may be consid-
Table 1 – Summary of results.
N Median duration of diabetes (years) Median HbA1c ± SE (%) Median age (years) a
Mann–Whitney U.
Type I patients (T1DM)
Type 2 patients on insulin (T2I)
Type 2 patients on SU (T2SU)
31 6 (IQR 5–14) 8.2 ± 0.5 46 (IQR 36–56)
23 11 (IQR 7–16) 8.5 ± 0.6 70.5 (IQR 61–78)
10 3 (IQR 0–6) 6.6 ± 0.9 79 (IQR 76–83)
p valuea T1DM vs T2SU
p valuea T2I vs T2SU
<0.0001 <0.0001
<0.001 0.01
p r i m a r y c a r e d i a b e t e s 4 ( 2 0 1 0 ) 61–63
ered as possible alternatives to SU therapy if hypoglycaemia is a concern [3]
Conflict of interest [4]
None to declare.
references
[1] National Institute of Clinical Excellence, Clinical Guideline 66. The Management of Type 2 Diabetes, 2008. [2] L.C. Hay, E.G. Wilmshurst, et al., Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2
[5]
[6]
63
diabetes mellitus: the results of continuous glucose monitoring, Diabetes Technol. Ther. 5 (1) (2003) 19–26. A.M. Jennings, R.M. Wilson, G. Fulcher, Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents, Diabetes Care 12 (3) (1989) 203–208. G. The Action to Control Cardiovascular Risk in Diabetes Study, Effects of intensive glucose lowering in Type 2 diabetes, N. Engl. J. Med. 358 (24) (2008) 2545–2559. E.S. Huang, Q. Zhang, et al., The effect of comorbid illness and functional status on the expected benefits of intensive glucose control in older patients with type 2 diabetes: a decision analysis, Ann. Intern. Med. 149 (1) (2008) 11–19. J.M. Nelson, K. Dufrax, P.F. Cook, The relationship between glycemic control and falls in older adults, J. Am. Geriatr. Soc. 55 (12) (2007) 2041–2044.
Contents lists available at ScienceDirect
Primary Care Diabetes journal homepage: http://www.elsevier.com/locate/pcd
Brief report
Sulphonyurea as a cause of severe hypoglycaemia in the community Jen M. Ng ∗ , Duane D. Mellor, Ewan A. Masson, Belinda J. Allan Diabetes Centre, Michael White Centre, Hull Royal Infirmary, 220-226 Anlaby Road, Hull HU3 2RW, United Kingdom
a r t i c l e
i n f o
a b s t r a c t
Article history:
Introduction: Hypoglycaemia is a well recognised side effect of insulin and sulphonyurea
Received 12 October 2009
therapy in the treatment of, patients with diabetes mellitus.
Received in revised form
Methods: We performed a retrospective analysis of patients who developed severe hypogly-
14 December 2009
caemia in Hull and, East Yorkshire, United Kingdom over a 4-month period to assess the
Accepted 15 December 2009
different therapies that contribute the most to the problem and the patient groups who are
Available online 12 January 2010
at greatest risk. Results: Of the 75 patients with diabetes mellitus who developed severe hypoglycaemia, 61
Keywords:
(80%) were taking, insulin, 5 in combination with metformin. Ten (13%) patients were taking
Hypoglycaemia
SU therapy; 5 in, combination with metformin, 2 in combination with a thiazolidinedione
Sulphonylurea
and 1 in combination with, insulin. When the SU-treated and non-SU treated groups were compared, patients taking SU therapy were, significantly older and had significantly lower HbA1c levels. Conclusions: All patients taking SU and insulin treatment are potentially at risk of developing hypoglycaemia. Our, analysis shows that almost 15% of patients in our region who suffered from severe hypoglycaemia, were on SU therapy. Patients in this group were older and had lower levels of HbA1c. Whilst national HbA1c targets may be useful for clinicians to define glycaemic targets for their, population, this has to be tempered by what is in the best interests of the patient and not what is, dictated by the Quality and Outcomes Framework. Possible alternatives to SU therapy should be, considered especially if hypoglycaemia is a concern. © 2009 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
1.
Introduction
Hypoglycaemia is a well recognised side effect of insulin and sulphonyurea therapy in the treatment of patients with diabetes mellitus. Recent National Institute for Health and Clincial Excellence (NICE) clinical guidelines recommend that patients with Type 2 Diabetes Mellitus (T2DM) are given advice regarding hypoglycaemia when starting
∗
insulin or sulphonylurea (SU) therapy [1]. SU and insulin therapy have been associated with an increased risk of hypoglycaemia particularly in a population who have tight glycaemic control [2,3]. We performed a retrospective analysis of patients who developed severe hypoglycaemia in Hull and East Yorkshire, United Kingdom over a 4-month period to assess the different therapies that contribute the most to the problem and the patient groups who are at greatest risk.
Corresponding author. Tel.: +44 01482 675314; fax: +44 01482 675395. E-mail address: [email protected] (J.M. Ng). 1751-9918/$ – see front matter © 2009 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.pcd.2009.12.001
62
2.
p r i m a r y c a r e d i a b e t e s 4 ( 2 0 1 0 ) 61–63
Methods
All episodes of hypoglycaemia which involve the ambulance service in our Trust are reported to the local diabetes service within 72 h with patient consent. Hypoglycaemic episodes that occur in the hospital A&E are fed back within 72 h to enable rapid patient review and follow up. We included all reported episodes of severe hypoglycaemia from these sources over the period of December 2008 to March 2009 inclusive. We defined severe hypoglycaemia in this case as any hypoglycaemic event that required the intervention of the emergency services.
structured education (‘Living With Diabetes’) which includes education on the side effects of common treatments for type 2 diabetes (including SUs). However, this education is not necessarily given at a point when SU initiation is being considered. One patient on SU therapy (10%) received education on hypoglycaemia recognition and treatment but only because he was being commenced on insulin. Virtually all patients receiving SU treatment would have had this initiated in primary care and it was not possible for us to assess what information had been given to the patient at this point regarding hypoglycaemia recognition and treatment.
4. 3.
Discussion
Results
A total of 76 patients suffered severe hypoglycaemia over the 4-month study period. Seventy-three episodes occurred at patient’s residences (i.e. home, residential home, etc.) whilst 3 episodes occurred outside. There were no other serious adverse events associated with the hypoglycaemic event. The median age of patients was 63 years (IQR 43–78 years); 40 were male and 36 female. The median HbA1c was 8.1 ± 0.3 SE%. Thirty-one (40.7%) patients had type 1 diabetes (T1DM) and 33 (43.4%) had T2DM. In 11 (14.4%) cases diabetes type was not recorded. One patient without diabetes suffered hypoglycaemia due to liver failure and was excluded from the study. Of the 33 patients with T2DM, 23 (69.7%) were taking insulin of which 5 (15.1%) were in combination with metformin. Ten (30.3%) patients were taking SU therapy; 5 (15.1%) in combination with metformin, 2 (6%) in combination with a thiazolidinedione and 1 (3%) in combination with insulin. Therapy in 3 patients was not recorded. No patient presented more than once during the study period. The results of the analysis are summarised in Table 1. All HbA1c readings were obtained within 3 months of the hypoglycaemic event. When the SU-treated and non-SU treated groups were compared, patients taking SU therapy were significantly older and had significantly lower HbA1c levels. Five patients in the SU group had HbA1c levels < 6.0%. All patients taking SU and insulin treatment are potentially at risk of developing hypoglycaemia [2,3]. Our analysis shows that almost 15% of patients in our region who suffered from severe hypoglycaemia were on SU therapy. Patients in this group were older and had lower levels of HbA1c. Prior to commencing insulin therapy, all patients receive education on the recognition and management of hypoglycaemia from the diabetes specialist nurse. In our area, all patients newly diagnosed with type 2 diabetes are offered
It has been suggested that a lower HbA1c may increase an individual’s risk of cardiac death [4], particularly in the later stages of their disease. In addition, the risk: benefit of tight glycaemic control appears to potentially favour risk in those aged 75 or more [5] in terms of falls and may not improve life expectancy [6] or quality of life. The personal as well as the financial cost associated with morbidity secondary to severe hypoglycaemia must also be considered. Whilst national HbA1c targets may be useful for clinicians to define glycaemic targets for their population, this has to be tempered by what is in the best interests of the patient and not necessarily what is dictated by the Quality and Outcomes Framework. The NICE guidance recommends that patients try to maintain their target HbA1c but recognises that this target may be above the recommended national target [1]. It is therefore vital that clinicians responsible for diabetes management are ready to strike a balance between good glycaemic control whilst taking into consideration potential side effects and the impact this may have on the individual concerned. The importance of patient education in recognising and treating hypoglycaemia is vital. The importance of patient education in recognising and treating hypoglycaemia is vital. Healthcare professionals initiating any therapy for diabetes mellitus must be aware of the potential side effects and counsel patients accordingly. All patients who are commenced on insulin therapy are referred for education with the diabetes specialist nurse. Similarly, education should be a consideration prior to commencing patients on medications that can evoke hypoglycaemia in particular SU therapy due to its potentially severe side effects. The emergence of new therapies in the treatment of T2DM such as gliptins and GLP-1 analogues in combination with conventional oral agent glucose-lowering therapy have lower risks of hypoglycaemia. Therefore these therapies may be consid-
Table 1 – Summary of results.
N Median duration of diabetes (years) Median HbA1c ± SE (%) Median age (years) a
Mann–Whitney U.
Type I patients (T1DM)
Type 2 patients on insulin (T2I)
Type 2 patients on SU (T2SU)
31 6 (IQR 5–14) 8.2 ± 0.5 46 (IQR 36–56)
23 11 (IQR 7–16) 8.5 ± 0.6 70.5 (IQR 61–78)
10 3 (IQR 0–6) 6.6 ± 0.9 79 (IQR 76–83)
p valuea T1DM vs T2SU
p valuea T2I vs T2SU
<0.0001 <0.0001
<0.001 0.01
p r i m a r y c a r e d i a b e t e s 4 ( 2 0 1 0 ) 61–63
ered as possible alternatives to SU therapy if hypoglycaemia is a concern [3]
Conflict of interest [4]
None to declare.
references
[1] National Institute of Clinical Excellence, Clinical Guideline 66. The Management of Type 2 Diabetes, 2008. [2] L.C. Hay, E.G. Wilmshurst, et al., Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2
[5]
[6]
63
diabetes mellitus: the results of continuous glucose monitoring, Diabetes Technol. Ther. 5 (1) (2003) 19–26. A.M. Jennings, R.M. Wilson, G. Fulcher, Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents, Diabetes Care 12 (3) (1989) 203–208. G. The Action to Control Cardiovascular Risk in Diabetes Study, Effects of intensive glucose lowering in Type 2 diabetes, N. Engl. J. Med. 358 (24) (2008) 2545–2559. E.S. Huang, Q. Zhang, et al., The effect of comorbid illness and functional status on the expected benefits of intensive glucose control in older patients with type 2 diabetes: a decision analysis, Ann. Intern. Med. 149 (1) (2008) 11–19. J.M. Nelson, K. Dufrax, P.F. Cook, The relationship between glycemic control and falls in older adults, J. Am. Geriatr. Soc. 55 (12) (2007) 2041–2044.