Interview Date: June 2009
Lead author Dr. Bo Ahrén's record in Essential Science
Indicators includes 222 papers, the majority of which are classified in
the fields of Clinical Medicine and Biology & Biochemistry, cited a
total of 5,030 times between January 1, 1999 and February 28, 2009. Three
more of these papers are also key papers in the same Research Front Map.
Dr. Ahrén is the Dean of the Faculty of Medicine at Lund University
In the interview below,
ScienceWatch.com talks with Dr. Ahrén about
this paper and its impact on the research
Would you please describe the significance of
your paper and why it is highly cited?
The paper published in 20021 was the first clinical study in
which an inhibitor of dipeptidyl peptidase-4 (DPP-4) was examined in
subjects with type 2 diabetes. The study was the proof-of-concept of the
strategy to inhibit DPP-4 as a therapy in type 2 diabetes. The study was
performed at five different research centers in Sweden. It had a four-week
duration and showed that a DPP-4 inhibitor reduced fasting and 24-hour
glucose levels as well as HbA1c levels. Furthermore, the paper also showed
that DPP-4 inhibition is safe and tolerable.
"The rapid and extensive development
of DPP-4 inhibition as a therapy of type 2
diabetes, which is now used clinically
worldwide, therefore had its clinical start
in this publication."
This paper initiated a huge interest in this concept of treating subjects
with type 2 diabetes and has since been followed by a number of studies and
also development of several DPP-4 inhibitors. Some of these DPP-4
inhibitors (vildagliptin and sitagliptin) have now reached the market,
whereas others are in late phase III and/or have been filed2.
How did you become involved in this research, and
were there any particular successes or obstacles that stand
DPP-4 inhibition as a therapy is based on the characteristic of this enzyme
to inactivate the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1
is an incretin hormone which has islet effects of potential interest to
perturb in type 2 diabetes, such as stimulation of insulin secretion,
inhibition of glucagon secretion, and also, at least in rodents, an
increase in ß-cell mass. I had been working on this gut hormone since
the mid 1980s and on DPP-4 inhibition ten years before this publication. In
1992, GLP-1 had already been suggested as a potential novel therapy of type
2 diabetes in a study which was performed together with Suad Efendic and
Mark Gutniak in Stockholm3. A problem in this development was
that GLP-1 was rapidly inactivated, which made native GLP-1 unrealistic as
a therapy. This was overcome by acknowledging that the inactivation of
GLP-1 is executed by DPP-4, and therefore DPP-4-resistant GLP-1 receptor
agonists or DPP-4 inhibitors are therefore possibilities for GLP-1-based
therapy in the clinic.
Where do you see your research and the broader
field leading in the future? What are the implications of your work
for this field?
After the establishment that it was DPP-4 which was responsible for the
rapid inactivation of GLP-1, it was suggested that DPP-4 inhibition would
be an alternative approach to use the therapeutic promises of GLP-1 without
using native GLP-14. Therefore, since the late 1990s, DPP-4
inhibition has been explored, and we showed that this was feasible in
animals5. Thereafter, it was natural to examine this in subjects
with type 2 diabetes, which was the study initiated by Novartis Pharma,
which resulted in the 2002 publication1. The rapid and extensive
development of DPP-4 inhibition as a therapy of type 2 diabetes, which is
now used clinically worldwide, therefore had its clinical start in this
1 Ahrén B, Simonsson E, Larsson H,
Landin-Olsson M, Torgeirsson H, Jansson PA, Sandqvist M, Båvenholm P,
Efendic S, Eriksson JW, Dickinson S, Holmes D, "Inhibition of dipeptidyl
peptidase IV improves metabolic control over a 4 week study period in type
2 diabetes," Diabetes Care 25:869-75, 2002.
2 Ahrén B, "Dipeptidyl peptidase-4
inhibitors—clinical data and clinical implications," Diabetes
Care 30:1344-50, 2007.
3 Gutniak M, Ørskov C, Holst J,
Ahrén B, Efendic S, "Antidiabetogenic effect of glucagon-like
peptide-1 (7-36)amide in normal subjects and patients with diabetes
mellitus," N. Engl. J. Med. 326:1316-22, 1992.
4 Holst JJ, Deacon CF, "Inhibition of the
activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes,"
Diabetes 47:1663-70, 1998.
5 Ahrén B, Holst JJ, Mårtensson H,
Balkan B, "Improved glucose tolerance and insulin secretion by inhibition
of dipeptidyl peptidase IV in mice," Eur.
J. Pharmacol. 404:239-45, 2000.
Faculty of Medicine
Bo Ahrén's current
In Essential Science Indicators, with 300 cites:
Wallenius V, et al., "Interleukin-6-deficient mice
develop mature-onset obesity," Nature Med. 8(1):
75-9, January 2002.
In the Research Front Map
Drug Treatment for Type 2 Diabetes), with 224 cites:
Ahrén B, et al., "Inhibition of dipeptidyl
peptidase IV improves metabolic control over a 4-week study
period in type 2 diabetes," Diabetes Care 25(5):
869-75, May 2002. 224 cites.
Essential Science Indicators from
KEYWORDS: DIPEPTIDYL PEPTIDASE 4 INHIBITOR, DDP-4, TYPE 2
DIABETES, THERAPY, MULTICENTER TRIAL, FASTING GLUCOSE, 24-HOUR
GLUCOSE, HBA1C, VILDAGLIPTIN, SITAGLIPTIN, GLUCAGON-LIKE PEPTIDE-1,
GLP-1, INSULIN SECRETION, GLUCAGON SECRETION, BETA-CELL