INTRODUCTION:

Diabetes is a multisystem disorder with complex pathogenesis with long term complications in both urban and rural communities in India^l,2,3.

The American Diabetes Association [ADA] recommends regular screening of atrisk individuals based on the defined criteria⁴. Type 2 diabetes evolves over years making difficult in identification unless blood sugar isscreened at least once in ayear for individuals more than 30 years of age. The isolated postprandial hyperglycaemia is an individual risk factor for cardiovascular morbidity andmortality^5,6,7. The treatment of the type 2 diabetes mellitus[DM] should be started as early aspossible to postpone microvascular and macrovascular complications^8,9,10. Metformin isconsidered as the gold standard in the treatment of prediabetes and ongoing disease with orwithout adding insulin¹¹. Sulfonylurea is considered as the added option if monotherapy with metformin fails and being the insulin secretagogue it works in reducing fasting, postprandial sugar and HbA1clevel^12,13,14. As per the recent ADA recommendation Alpha Glycosidase Inhibitors [AGI] like acarbose, voglibose (or) any DPP-4 inhibitors like vildagliptin, saxagliptin, teneligliptin will be the option as 2^nd or 3^rd line therapy in the management of the disease^15,16,17. The STOP-NIDDMtrial demonstrates the effect ofalpha glucose inhibitors in type-2 DM management¹⁸. The U.K. prospective diabetic study supported the advantage of acarbose or voglibose especially for isolated postprandial blood sugar¹⁹. Voglibose is comparatively better than acarbose incase of efficacy, cost effectiveness and gastrointestinal side effects²⁰. Thus, AGI possess excellent safety profile without hypoglycaemia, no weightgain and a marked reduction in cardiovascular morbidity²¹.

The dipeptidyl-peptidase 4 inhibitors (DPP-4) enhances insulin secretion and reducing glucagonlevel. The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) andAmerican Association of Clinical Endocrinologists (AACE) with recently published algorithm places DPP-4 inhibitors as the top choice after metformin^22,23,24,25.

Teneligliptin was approved and marketed in Japan since 2012²⁶. The efficacy and safety iswith the database of Japan Pharmaceuticals and Medical Devices Agency [PMDA]²⁷. InIndia, the utilization of teneligliptin is much more common thanother gliptins due to its efficacy, moderate cost and considered one of the suitable add on therapy after sulfonylureas.The side effects are found to be tolerable in our Indian population as per recent studies.

Hence a comparative randomized control trial was planned to find out the efficacy and safety of teneligliptin and voglibose as an add on therapy in type to diabetes mellitus patients.

AIM:

To compare the efficacy and safety of teneligliptin and voglibose and in reducing blood sugar levels, glycosylated haemoglobin A1c (HbA1c) andpostponing the microvascular complications of diabetes when added to metformin and glimepiride.

Primary objective:

Reduction in Fasting Blood Sugar(FBS), Post-Prandial Blood Sugar (PPBS) and Glycosylated Haemoglobin A1c (HbA1c)in treatment groups.

Secondary objective:

1. To compare the effectiveness of reducing microalbuminuria in the trial group.

2. To report any adverse effects of the comparative drugs.

METERIALS AND METHODS:

Study Design: A Prospective Randomized Cross Sectional Control Trial

Study Centre: Department of Medicine, VMKVMC and H, Salem.

Study Population:

Atotal of 80 diabetic patients were categorized into 2 groups .

GroupA -40patients receivedglimepiride 2mg OD withmetformin 500mg BD and teneligliptin 20 mg OD.

Group B-40 patients receivedglimepiride 2mg OD with metformin500mg BD andvoglibose 0.3mg BD.

M ETHODOLOGY:

This prospective randomized cross sectional control trial was carried out in a tertiarycarecentre, Salem, Tamilnadufor a period of one year between Feb 2020 to Jan 2021. Around80 patients with diagnosis of Type 2 DM withuncontrolled blood sugar who were already on glimepiride 2mg OD+ metformin 500mg BD were be enrolled for the study and randomly assigned by chance[ flipping the coin]. Male and femalepatients with the age group of 40 - 70 years based on the clinical examination and appropriateinvestigations were included. The study group included diabetics patients with HbA1c level between 7 to 9, BP of > 140/90 and <150/100 with early changes in microalbuminuria.

The two groups were investigated for FBS, PPBS, HbA1c, urine routine examination, microalbuminuria, blood urea and creatinine just after enrolment.The personal history about life stylehabits including alcoholism and tobacco consumption was obtained in all patients. Both the groups were instructed to take the new medication and report to the doctor in case of anyadverse effects. Patients were instructed to take glimepiridehalf an hour before food in the morning and other drugs after the food. Patients were advised totake medications properlywithout skipping the dose and it were cross checked at the end of 12^thweek and 24^th week. Informed consent was obtained in all the patients in vernacular language. The research protocol wassubmitted to Institutional Ethical Committeeand approved for the same.

Inclusion Criteria:

1) Patients with a diagnosis of type II DM with HbA1c 7 to 9 % after confirming withhistory andrelevant

investigations.

2) Both sexes aged between 40 to 70years

3) Associated mild hypertension>140/80mmHg but less than 150/100mmHg

4) Had already treated with glimepiride 2mg, OD withmetformin 500mg, BD

Exclusion Criteria:

l. Type 1 diabetes mellitus.

2. Drugs other than the above prescribed oral hypoglycaemic drugs or insulin.

3. Had incidences ofdiabetic ketoacidosis or hyperosmolar coma during the study period.

4. Pregnancy and lactating mothers.

5. Other co-morbid conditions like thyroid disorders, anaemia, proven hypertension ontreatmentischemic

heart disease and stroke were excluded.

Study visits and follow up:

The study consists of a screening visit and follow up visitsat the end ofthird month and six month.

Laboratory Parameters:

The following investigations such as FBS, PPBS, HbA1c,urine routine examination, microalbuminuria, blood urea and creatinine were carried outbefore the start-up of the study and at the end of third month and six month of study period.

Statistical Analysis:

Data were tabulated in Excel sheet and statistical analysis was done by using Epi info software. Basic demographic data like age and sex distribution were expressed as frequencies and percentages. Comparison of means between the two groups were analysed by usingANOVA (Analysis of Variance). APvalue of<0.05 was considered as statisticallysignificant.

RESULTS:

As per the inclusion criteria totally 80 patients were included, there were equal distribution of maleand female patients with the ratio being 1:1 in our study population. Out of which 52.5% were male patients and 47.5% were female patients in group I with 50% were male patients 50 % female patients in group II. The mean age were55.93 years inteneligliptin group and 55.43 years in voglibose group. Majority of the patients were between 41 to 50 years of age. The age and gender wise distribution of both groups were depicted in Table 1.

Figure –I showed age and sex wise distribution of both groups

Table: 2 Fasting blood sugar level of Group I and Group II at third month and six month

Fasting blood sugar	Group I (Teneligliptin)		Group II (Voglibose)		P-Value
Fasting blood sugar	Mean	SD	Mean	SD
3^rd Month	136	±19.6	133	±14.03	0.000
6^th Month	128	±14.89	127	±12.48	0.039

Table -2 showedfasting blood sugar level of Group I and Group II at the end of third month and end of six month. The fasting blood sugar is reduced in teneligliptin group at the end of 3^rd and 6^th month and it isstatistically significant.

At the end of 3^rd month (f -ANOVA Value=10.892), P=0.000,At the end of 6^th month (f -ANOVA Value= 2.304),P=0.039

SD-Standard Deviation

Table: 3 Post prandial blood sugar level of Group I and Group II at third month and six month

Post prandial blood sugar	Group I (Teneligliptin)		Group II (Voglibose)		P-Value
Post prandial blood sugar	Mean	SD	Mean	SD	P-Value
3^rd Month	208	±24.53	213	±18.53	0.000
6^th Month	176	±17.69	175	±12.96	0.034

Table- 3 showed post prandial blood sugar level of Group I and Group II at the end of third month and end of six month. The post prandial blood sugar level is reduced in teneligliptin group at the end of 3^rd month and 6^th month and it is statistically significant.

At the end of 3^rd month (f-ANOVA Value=10.825),P = 0.000, At the end of 6^th month (f -ANOVA Value= 2.290)P = 0.034

*SD-Standard Deviation

Table: 4 Blood urea level of Group I and Group II at third month and six month

Blood urea level	Group I (Teneligliptin)		Group II (Voglibose)		P-Value
Blood urea level	Mean	SD	Mean	SD	P-Value
3^rd Month	26	±5.64	23.25	±4.82	0.000
6^th Month	21	±4.25	22	±3.97	0.013

Table-4 depicted blood urea level of Group I and Group II at third month and six month of studyperiod. The blood urea level is normal in both the test groups at the end of third and six month.

At the end of 3^rd month (f -ANOVA Value= 5.61), P=0.000, At the end of 6^th month (f-ANOVA Value=3.42), P=0.013

SD-Standard Deviation

Table: 5 Creatinine level of Group I and Group II at third month and six month

Creatinine level	Group I (Teneligliptin)		Group II (Voglibose)		P-Value
Creatinine level	Mean	SD	Mean	SD	P-Value
3^rd Month	0.06	±0.17	0.54	±0.15	0.141
6^th Month	0.46	±0.13	0.6	±0.16	0.254

Table -5 depicted creatinine levelof Group I and Group II at third month and six month of study period. At the end of third monthand six month the creatinine level is within the normal limit in both groups.

At the end of 3^rd month (f-ANOVA Value=1.789), P=0.141, At the end of 6^th month (f-ANOVA Value=1.385), P=0.254

*SD-Standard Deviation

Table: 6 HbA1c level of Group I and Group II at base line, third month and six month

HbA1c Level	Group I (Teneligliptin)		Group II (Voglibose)		P-Value
HbA1c Level	Mean	SD	Mean	SD
Baseline	8.2	±0.49	8.1	± 0.29	0.312
3^rd Month	7.5	±0.28	7.3	±0.27	0.008
6^th Month	6.9	±0.24	6.9	±0.22	0.073

Table - 6 depicted HbA1c level of Group I and Group II at base line , third month and six month of study period. The HbA1c level is reduced in both the groups. The HbA1c reduction is statistically significant at the end of 3^rd month for teneligliptin group whereas no significant difference was observed at the end of 6^th month in both groups.

Figure 2: Shows mean level of HbA1c at base line, third month and six month. Both groups showed significant reduction in HbA1c.

Table: 7 Reduction of microalbuminuria level among the two groups of patients

Microalbuminuria Level	Number of patients with Microalbuminuria in Group I (Teneligliptin)	Number of patients with Microalbuminuria in Group II (Voglibose)
Baseline	15	15
3^rd Month	4	12
6^th Month	0	10

The microalbuminuria reduction is comparatively more in teneligliptin group when compared to voglibose group.

Table: 8 Occurrence of various adverse events among the two groups of patients

ADR	Group I (Teneligliptin)		Group II (Voglibose)
ADR	n=40	Percentage %	n=40	Percentage %
Dizziness	1	2.5%	-
Nausea	1	2.5%	2	5%
Flatulence	1	2.5%	5	12.5%
Constipation	-		5	12.5%
Total	3	7.5%	12	30%

N=No of subjects; ADR Adverse Drug Reaction

The GIT disturbances are more seen in voglibose group and compared to the competitor.

DISCUSSION:

In this prospective randomized controlled trial a total of 80 patients were included and divided into two groups of 40 patients each.Group I received teneligliptinand group II received voglibose along with glimepiride and metformin.Patients were followed up every month for six months with baseline investigations were repeatedat the end of 3rdand 6^th month.

DPP-4 inhibitors appear to be 2^nd line oral hypoglycaemic agent next to sulfonylureas.Teneligliptin the drug from Japan appears to have beneficial effects on beta cells and neutrality on body weight which does not need dose adjustment on renal diseases.It has been documented that the probable pathogenesis of albuminuria with higher urinary micro vesicles²⁸. Our study showed a reduction in microalbuminuria in our patients as teneligliptin and has a nephroprotective effects with an increase in GLP-1 level and improved histological changes. Our study is supported by Leena Varghese et aland Wei Jing Liuetal. where teneligliptin lowered glomerular, tubulointerstitial and vascular lesions in diabetic rats^29,30. A more recent study by Peter Vavrinec et.al. explained vildagliptin decreases glomerular sclerosis and arteriolar constriction to normal levels³¹. Also at this juncture, it is necessary to make a statement that alogliptinand sitagliptin reduced albuminuria in zucker diabeticrats^32,33,34,35. The author also concluded the improvement in renal status was not due to hypoglycaemic effects.

A significant reduction in FBS, PPBS, HbA₁c is seen in both the groups, where teneligliptin has a favourable glucose reduction along with voglibose. This is supported by Cyrus V Desouzaet.al but voglibose in comparison has less incidence of flatulence, abdominal pain when compared to acarbose and miglitol^36,37,38. Our study showed a less incidence of GIT side effects in voglibose which is supported by the above studies.

Teneligliptin is associated with improvement of Liver function and endothelial function^39,40. Our study demonstrated both teneligliptin and voglibose reduces HbA1c but the magnitude of reduction wassimilar in both the groups.

Asystolic blood pressure was reduced in teneligliptin group probably due to nitric oxide generation and vasorelaxation, but not in voglibose group. Voglibose reduces post prandial hyperglycaemia, it has a strong cardio protective action where by oxidative stress and dysfunction is seen with high blood sugar^41,42. Since elevated HbA1c is a marker of cardiovascular complications.

CONCLUSION:

Our study concludes that teneligliptin is better than voglibose as the 2^nd line add on therapy to sulphonylureas, metformin or insulin.

ACKNOWLEDGEMENTS:

Authors would like to acknowledge Vinayaka Mission’s Research foundation (Deemed to be University) Salem,for funding and supporting the project, study participants and technical staffs who helped to complete the research successfully.

FUNDING:

This research project is funded by Vinayaka Mission’s Research foundation (Deemedto be University), Salem.

CONFLICT OF INTEREST:

None declared.

Ethical approval: The study was approved by the Institutional Ethics Committee of VMKVMC and H,Salem.Tracking No. VMKVMC and H/IEC/19/100

REFERENCES:

1. Ramachandran A et al. The Indian Diabetes Prevention Programme shows that life style modification and metforminprevent type 2 diabetes in Asian Indian subjects withimpaired glucose tolerance (IDPP-1). S Diabetologia. 2006; 49(2): 289-297.doi: 10.1007/s00125-005-0097-z. Epub 2006 Jan 4.

2. Ramachandran A etal. Diabetes in South -East Asia: an update: Diabetes Resp Clinpractice. 2014; 103(2):231-237.DOI: 10.1016/j.diabres.2013.11.011.

3. Sincy Wilson, Sr. Symphoria. A Study to assess the effect of awareness Programme on Compliance to Insulin Therapy among Patients with Diabetes Mellitus (DM) in a Selected Community Health Centre, Thrissur District. Asian J. Nur. Edu. and Research. 2016; 6(4): 464-470.DOI: 10.5958/2349-2996.2016.00087.2.

4. Helena W Rodbard. etal. American Association of Clinical Endocrinologists medical guidelines for clinical practice for management of diabetes mellitus, AACE Diabetes Mellitus Guidelines.Endocrine Practice. 2007; 13 (Suppl 1).

5. D M Nathan etal. The epidemiology of cardiovascular disease in type 2 diabetes mellitus how sweet it is or is it?. Lancet. 1997; 350(1): 4-9.doi: 10.1016/s0140-6736(97)90021-0.

6. Healy JL. Pathogenesis of type 2 diabetes in type 2 diabetes mellitus. An evidence-based Approach to Practical Management. NJ Human Press. 2008: 17-33.

7. Adler Al et al. Association of systolic pressure with microvascular and macrovascularcomplications of type 2 diabetes (UKPDS 36): prospective observational study.BMJ. 2000; 321 (7258): 412-419. doi: 10.1136/bmj.321.7258.412.

8. Vijay VR ,Samundy Kumbhakar. A Descriptive Study to assess the Lifestyle Practices of Diabetic Patients with Respect to Glycemic Control. Asian J Nur Edu and Research. 2016; 6(4): 429-432. DOI:10.5958/2349-2996.2016.00081.1.

9. Stamler J et al. diabetes,other risk factors and 12 years cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care. 1993; 16(2): 434-44. doi: 10.2337/diacare.16.2.434.

10. Mudaliar S. New frontier's in the management of type 2 diabetes mellitus. Indian JMed Resp. 2007; 125: 279-96.

11. HazarataliPanari, Vegunarani.M. Study on Complications of Diabetes Mellitus among the Diabetic Patients. Asian J Nur Edu and Research. 2016; 6(2): 171-182. DOI: 10.5958/2349-2996.2016.00032.X.

12. Riddle M. Combining sulfonylureas and other oral agents: AMJMed. 2000; 108: 15-22.DOI: 10.1016/s0002-9343(00)00338-7.

13. Silvio E Inzucchi. Oral antihyperglycemic therapy for type 2 diabetes. Scientific review. JAMA. 2002; 287: 360-372.doi: 10.1001/jama.287.3.360.

14. Sreedevi K. A study to assess the effectiveness of structured Teaching Programme on self-care management of patients with type 2 Diabetes mellitus and Evaluation of prognosis in selected Hospitals. Asian Journal of Nursing Education and Research. 2020; 10(4): 427-431. DOI: 10.5958/2349-2996.2020.00091.9.

15. Skyler Js etal.Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials. Diabetes Care. 2009; 32: 187-192. doi: 10.2337/dc08-9026

16. Maruthur NM. Singh S et.al comparative effectiveness and safety of medications fortype 2 diabetes; Ann. Intern Med 2011. 154: 602-613.doi: 10.7326/0003-4819-154-9-201105030-00336.

17. Ankita et al. Identification of Dipeptidyl peptidase-4 (DPP-4) inhibitors as Potential Antidiabetic agents using Molecular docking study. Research J Pharm and Tech. 2020; 13(11): 5257-5262. DOI: 10.5958/0974-360X.2020.00919.1.

18. Deacon CF: Dipeptyl peptidase 4 inhibitors in the treatment of type 2 diabetes; acomparative review. Diabetes ObesMetab. 2011; 13 (1):7-18.doi: 10.1111/j.1463-1326.2010.01306.x.

19. A I Adler et al., Prospective Diabetes Study Group. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes: ProspectiveObservational Study BMJ. 2000: 321: 412-419.doi: 10.1136/bmj.321.7258.412.

20. Dr. Amita Jindal et al. Efficacy and Safety of Voglibose as an add on triple drug inpatients of type 2 diabetes mellitus uncontrolled with glimepiride and metformin inPunjabi population.Indian Journal of Basic and Applied Medical Research. 2014; 3(3): 111-116.

21. American diabetes management. Medical Management of type 2 diabetes. Alexandria. 2012.

22. Singh AK. Incretin response in Asian type 2 diabetes: Are Indians different?.Indian J Endocrinol Metab. 2015; 19(1): 30-38.doi: 10.4103/2230-8210.146861

23. Eiji Kutohetal. Teneligliptin as an initial therapy for Newly Diagnosed Drug Naive Subjectswith Type 2 Diabetes, JClin Med Res. 2014; 6(4): 287-294. doi: http://dx.doi.org/10.14740/jocmr1841e

24. Sharma Priya, Malik Sujeeta. Effectiveness of Structured Teaching Programme on Fasting Blood Sugar among Patients with Type II Diabetes Mellitus in a selected Community Health Centre of Dadra and Nagar Haveli area. Int J Nur Edu and Research. 2019; 7(2): 170-172. DOI: 10.5958/2454-2660.2019.00034.6

25. Jeeva. S, Molly Babu. Assessment of self-care Practices of Diabetic Clients Regarding Management of type II Diabetes Mellitus at Selected Urban area of Bangalore, Karnataka. Int. J. Nur. Edu. and Research. 2016; 4(4): 449-455. DOI: 10.5958/2454-2660.2016.00083.1.

26. Eiji Kutoh et al. Teneliglipliptin as an initial therapy for Newly Diagnosed Drug Naïve subjects with type 2 diabetes. J Clin Med Res. 2014; 6(4): 287-94.doi: 10.14740/jocmr1841e

27. Pharmaceuticals and Medical Devices Agency Japan. Teneligliptin Review. 2012 April; .

28. Ai-li Sun et al. Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease. Diab. Vasc Dis Res. 2012; 9(4): 301-308. doi: 10.1177/1479164111434318. Epub 2012 Mar 2.

29. Leena Varghese et al. Teneligliptin as an add on Therapy to Oral Anti diabetic agents in type 2 Diabetes Mellitus. Research J Pharm and Tech. 2020; 13(5): 2310-2314. DOI: 10.5958/0974-360X.2020.00416.3.

30. Wei Jing Liu et al. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin –induced diabetic rats. J Pharmacol ExpTher. 2012; 340(2), 248-255. doi: 10.1124/jpet.111.186866. Epub 2011 Oct 24.

31. Peter Vavrinec et al. Vildagliptin restores renal myogenic function and attenuates renal sclerosis independently of effects on blood glucose or proteinuria in Zucker diabetic fatty rat. Curr Vasc Pharmacol. 2014; 12 (6): 836-844. doi: 10.2174/15701611113116660151.

32. Koji Sakata et al. Efficacy of alogliptin, a dipeptidyl peptidase- 4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE) - receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes. Diabetes Metab ResRev. 2013; 29 (8): 624-630.doi: 10.1002/dmrr.2437.

33. Sachiko Hattori. Sitagliptin reduced albuminuria in patients with type 2 diabetes. Endocr J. 2011; 58(1), 69-73. doi: 10.1507/endocrj.k10e-382. Epub 2010 Dec 28.

34. Markus L Alter et al. DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy. Kidney Blood Press Res. 2012; 36(1): 119-130. doi: 10.1159/000341487. Epub 2012 Oct 15.

35. Jingjing Li et al. The dipeptidyl peptidase-4 inhibitor sitagliptin protects against dyslipidemia-related kidney injury in Apolipoprotein E knockout mice. Int J Mol Sci. 2014; 15: 11416-11434.doi: 10.3390/ijms150711416.

36. Ishan Panchalet al.. Recent Advancement towards Treatment of Diabetes. Research J Pharmacology and Pharmacodynamics. 2010; 2(1):12-22.

37. Cyrus V Desouza et al.Diabetes and cardiovascular events. Diabetes Care. 2010; 33(6):1389-94.doi: 10.2337/dc09-2082.

38. Iwamoto yet al. Efficacy and safety of vildagliptin and voglibose in Japanese patients with type 2 diabetes; a 12 week, randomized, double blind, active controlled study. Diabetes Obesmetab. 2010;12 (8): 700-708.

39. Enrique Z. Fismanand Alexander Tenenbaum. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes.Fishman and Tenenbaum Cardiovasc Diabetol. 2015; 14: 129. DOI 10.1186/s12933-015-0294-0.

40. Geetha. V, Shrimant K. Sahu, C. Susila. Assess Quality of Life (QOL) and Glycemic Level among Type 2 Diabetic Patients in Global Hospital and Research Centre and its Units, Sirohi, Rajasthan. Asian J. Nur. Edu. and Research. 2017; 7(4): 577-582

41. Brown NJ. Cardiovasular effects of antidiabetic agents: focus on blood pressure effects of incretin - based therapies. J Am Soc Hypertens. 2012; 6: 163-8.

42. Marques,C. et al. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals. Mediators Inflamm. 2014; 2014: 538737. doi: 10.1155/2014/538737. Epub 2014 Apr 8.

Received on 13.12.2021 Modified on 23.10.2022

Research J. Pharm. and Tech 2023; 16(12):5906-5911.

DOI: 10.52711/0974-360X.2023.00957

Age group in years	Group I (Teneligliptin) N=40				Group II ( Voglibose) N=40
Age group in years	Male		Female		Male		Female
	N	Percentage (%)	N	Percentage(%)	N	Percentage(%)	N	Percentage(%)
41-50	2	5%	11	27.50%	6	15%	10	25%
51-60	7	17.50%	4	10%	8	20%	6	15%
>60	12	30%	4	10%	6	15%	4	10%
Total	21	52.5%	19	47.5%	20	50%	20	50%
Mean age	55.93				55.43