Defending champions Wolfsburg have comfortably booked their place in the second round of the DFB-Pokal with a 4-1 victory over Stuttgarter Kickers.
De Bruyne then made it 3-0 with a clever finish early in the second half, and Lhadji Badiane's goal 10 minutes from time proved to be nothing more than a consolation when Nicklas Bendtner scored to restored his side's three-goal lead.
© Getty Images
Klaas-Jan Huntelaar started the scoring in the fourth minute, and further goals from Matija Nastasic and Johannes Geis handed them a comfortable advantage after Branimir Bajic had been sent off for the home side for two bookable offences.
Di Santo had earlier missed a penalty at 1-0, but he made no mistake with an emphatic volley just after the hour mark and the rout was completed wen Leon Goretzka scored with five minutes remaining.
The striker was on hand to finish a patient passing move from a few yards out on 16 minutes, before Hakan Calhanoglu doubled the advantage with a penalty early in the second half.
The Frenchman took just 30 seconds to break the deadlock, before adding a second with a penalty after Meppen goalkeeper Benjamin Gommert had been sent off and he rounded off an impressive start with a third strike 11 minutes from time.
Simon Zoller scored a fourth late on as Koln started their bid for a first success in the competition for 23 years.
Viktor Skrypnyk's men were left frustrated for long spells, but Anthony Ujah made the crucial breakthrough before the interval in extra time with a powerful finish on the turn.
Wurzburger's brave challenge was ended in the second period when Fin Bartels sprinted clear and sent Werder through with a clever chipped finish.